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Latest revision as of 03:50, 22 January 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mohsen Basiri M.D. Syed Hassan A. Kazmi BSc, MD [2]

Overview

IgG deficiency is a form of hypogammaglobulinemia where the serum concentrations of one or more subclasses of IgG are diminished relative to other immunoglobulin isotypes, meanwhile total IgG concentration is noral. IgG deficiency is a laboratory finding that may be not associated with significant clinical presentations. The diagnosis of a clinically significant IgG deficiency needs evidence of antibody dysfunction in the form of recurrent infections and an inadequate response to vaccine challenge.

Most patients with IgG deficiency are usually asymptomatic. Symptoms of IgG deficiency may include the symptoms of recurrent sinopulmonary infections include otitis media, rhinosinusitis, and pneumonia or even more serious infections that can occur such as osteomyelitis, meningitis, septicemia, diarrhea, and skin infections.^[1]

IgG has four subclasses: IgG₁, IgG₂, IgG₃, and IgG₄. It is possible to have either a global IgG deficiency, or a deficiency of one or more specific subclasses of IgG.^[2]^[3] Since IgG1 forms about 70 percent of total IgG patients with IgG1 deficiency are classified as common variable immunodeficiency (CVID), a diagnosis that also needs reduced levels of IgA and/or IgM.

IgG2 subclass deficiency is the main clinically relevant form of IgG deficiency and is more prevalent among children than adults and is one of the most frequently identified disorders in children with recurrent infections in children or may present as transient hypogammaglobulinemia of infancy (THI), and may occur with or without additional reduction in IgA or IgM. IgG₃ deficiency is not usually encountered without other concomitant immunoglobulin deficiencies, and IgG₄ deficiency is very common but usually asymptomatic.^[4]

The diagnosis of a clinically significant IgG deficiency needs evidence of antibody dysfunction in the form of recurrent infections and an inadequate response to vaccine challenge. Management consists of immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines, aggressive treatment of other conditions predisposing to recurrent sinopulmonary infections and appropriate antibiotic therapy for infections and the use of prophylactic antibiotics for patients with repeated sinopulmonary infections.^[5]

Intravenous or subcutaneous immune globulin replacement should be reserved for patients with clearly impaired responses to protein and/or polysaccharide antigens and/or if the use of prophylactic antibiotics does not cause fewer infections or in patients with persistent and symptomatic chronic rhinosinusitis .^[6]

Historical Perspective

In 1952, Bruton reported a condition in an 8-year-old boy with recurrent episodes of bacterial infections and sepsis with the same serotypes of pneumococcus, while he had intact lymphoid tissue and B-cells but had decreased IgG levels and he had no antibodies against this pathogen.^[7]

In the 1960s, by the discovery of the IgG subclasses, further aspects of IgG deficiency and recurrent infection, were uncovered. and thrown new light on the understanding of IgG deficiencies subclasses, as isolated deficiencies (eg, selective IgG deficiency) or in association with deficiencies of other immunoglobulin types. Moreover, how even if the total IgG concentration is normal, deficiencies of one or more individual IgG subclasses, may be observed.^[8]

Classification

IgG deficiency may be classified according to individual IgG subclasses deficiency into four subtypes:

IgG1 deficiency : since IgG1 normally comprises almost two-thirds of the total serum IgG most patients with IgG1 deficiency have generalized hypogammaglobulinemia.Thus, most patients with significant IgG1 deficiency are classified as common variable immunodeficiency (CVID), a diagnosis that also requires decreased levels of IgA and/or IgM. Only patients with selective IgG1 deficiency and normal levels of total IgG should be diagnosed with IgG1 deficiency. Selective IgG1 deficiency with normal total IgG is uncommon.^[9]
IgG2 deficiency : is more prevalent among children than adults and is one of the most frequently identified disorders in children with recurrent infections.It has been described both as an isolated finding and in combination with IgG4 and/or IgA deficiency.^[10]^[11]
IgG3 deficiency : is more common in adults than children. It may occur alone or in combination with other subclass deficiencies, especially IgG1.^[12]
IgG4 deficiency : is considered to be common in the general population, meanwhile the majority of patients are asymptomatic. It may occur alone, or in combination with IgG2 deficiency, and with IgA-IgG2 deficiencies^[13]^[14]

Pathophysiology

Immunodeficiency diseases are described according to involvement one or more of the 4 major components of the immune system. These components are:

B-cell or humoral immunity is mediated by the immunoglobulins. There are five types or classes of immunoglobulin: IgG, IgA, IgM, IgD, and IgE. The IgG class of antibodies is composed of four different subtypes of IgG molecules called the IgG subclasses. These are designated IgG1, IgG2, IgG3, and IgG4. The term "IgG subclass deficiency" refers to a significant decrease in the serum concentrations of one or more subclasses of IgG in a patient whose total IgG concentration is normal ^[15]

PATHOGENESIS

The primary mechanisms underlying IgG subclass deficiency are unclear. Gene deletions, transcription errors, cytokine dysregulation, immunosuppressive therapy, and allotypic variations are some mechanisms that have been described :

Gene deletions: Heterozygous gene deletions cause the reduction in the serum concentration of the corresponding subclass. Deletions have been detected for genes C-gamma-1, C-gamma-2, and C-gamma-4 . Homozygous deletions of large portions of the immunoglobulin heavy chain gene, causes the absence of multiple immunoglobulin classes, and are also described. Such patients may have no detectable IgG1, IgG2, IgG4, IgA1, or IgE .^[16]
Transcription errors: Changes of germline transcription and limitation fragment length polymorphisms 5' of the S-gamma-4 loci within the gamma-chain constant region gene complex have been described among patients with IgG4 deficiency compared with controls.^[17]

Effect of allotype: Some IgG subclass deficiencies may be affected by allotype. The absence of the G2m(n) allotype and homozygosity for the G3m(g) and G3m(b) allotypes has been discoverd among Caucasian patients.^[18]

Causes

There are no established causes for IgG deficiency, and mechanisms underlying IgG subclass deficiency are unclear. Genetic, transcription errors, allotypic variations,and immunosuppressive therapy are some mechanisms that have been proposed.

Differentiating IgG deficiency from other Diseases

IgG deficiency must be differentiated from other diseases that cause recurrent episodic infections, especially recurrent sinopulmonary infections including otitis media, rhinosinusitis, and pneumonia. IgG defieciency should be differentiated from other disorders leading to hypogammaglobulinemia and defects of humoral immunity. The following conditions may be considered as differentials:^[19]^[20]^[21]^[22]^[23]^[24]^[25]^[26]^[27]^[28]^[29]^[30]^[31]^[32]^[33]^[34]^[35]^[36]^[37]^[38]^[39]^[40]^[41]^[42]^[43]^[44]^[45]^[46]^[42]^[47]^[48]^[49]^[50]^[51]^[52]^[53]^[54]^[55]^[56]^[57]^[58]^[59]^[60]^[61]^[62]^[63]^[64]^[65]^[66]^[67]^[68]


Disorder	Defect (Mechanism of Development)	Characteristic Features	Clinical Presentation	Laboratory Findings
X-Linked (Bruton) Agammaglobulinemia	Defect in tyrosine kinase gene (BTK) B cells fail to mature	X-linked recessive pattern of inheritance Increased prevalence in males	Recurrent bacterial and enteroviral infections after 6 months of age Pre-disposition to development of infections by encapsulated organisms Pre-disposition to development of Giardia infections Absent lymph nodes and tonsils	Normal CD19+ B cell count Decreased pro-B cells Increased pre-B cells Decreased immunoglobulins of all classes
Selective IgA Deficiency	Stem cell defect (Transferrable with marrow transplant) Lack of IL-4, IL-6, IL-7, IL-10, TGF-β, and IL-21 Mutations in transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI, TNFRSF13B)	Most common primary immune deficiency	Majority of the cases are asymptomatic Respiratory and gastrointestinal infections (mucosal infections) Associated with autoimmune diseases Atopy Anaphylaxis to IgA containing products	Serum IgA < 7 mg/dl Normal IgG and IgM levels
Common Variable Immunodeficiency	Defective B cell differentiation	May be acquired in 20-30 years of age	May present with other autoimmune diseases Associated with bronchiectasis Associated with lymphoma Associated with sinopulmonary infections (Bacterial, enteroviral and parasitic such as Giardia)	Decreased plasma cells Decreased immunoglobulins
Autosomal dominant hyper IgE syndrome (Job's Syndrome)	Defieciency of Th17 cells due to STAT3 mutation Impaired neutrophils to sites of infection	Distinctive coarse facies Cold (non-inflammatory) Staphylococcal abscesses Retained primary teeth Eczema		Increased levels of IgE Decreased levels of interferon gamma (IFN-gamma)
Severe combined immunodeficiency (SCID)	Defective interleukin-2 receptor gamma chain Adenosine deaminase deficiency Reg 1 and Reg 2 nonsense mutations	IL-2R disease is X-linked ADA deficiency and reg mutations are typically autosomal recessive	Failure to thrive Chronic diarrhea Thrush Recurrent bacterial, viral and protozoal infections Treatment is bone marrow transplant	Decreased T cell receptor excision circles (TRECs) Abscence of thymic shadow on chest X-Ray Absent germinal centers of lymph node biopsy Absent T cells on flow cytometry
Ataxia Telangiectasia	Defect in ATM gene DNA double stranded breaks leading to cell cycle arrest	Hypersensitivity to X-Rays	Triad of: Ataxia Spider angiomas (Nests of distended capillaries) IgA deficiency	Increased alpha fetoprotein (AFP) Decreased IgA, IgG and IgE Lymphopenia Cerebellar atrophy
Hyper IgM Syndrome	Defective CD40L (CD40 ligand) on Th cells leading to class switching defect	X-linked recessive pattern of inheritance	Severe pyogenic infections in early life Opportunistic infection with: Pneumocystis jiroveci Cryptosporidium Cytomegalovirus (CMV)	Increased IgM Decreased IgG, IgA and IgE No germinal centers
Wiskott-Aldrich Syndrome	Mutation in WAS gene T cells unable to reorganize actin microfilaments (microfilament defect)	X-linked recessive pattern of inheritance Increased risk of autoimmune disease and malignancy	Thrombocytopenic purpura Eczema Recurrent infections	Decreased to normal IgG and IgM Increased IgE and IgA Fewer and smaller platelets

Malignancy: can cause the reduction in the immunoglobulin production.^[69]

Viral infections: such as Epstein-Barr virus, HIV, cytomegalovirus are other causes of hypogammaglobulinemia.
Side effect of certain medications: Some drugs include systemic glucocorticoids, phenytoin, and carbamazepine, have been associated with IgG deficiency.^[70]
Other causes of primary humoral immunodeficiencies.
Smoking: may cause IgG2 subclass deficiency.^[71]
Protein-losing conditions: enteropathies, nephrotic syndrome, burns, and other traumas may cause abnormal loss of immunoglobulins.

Epidemiology and Demographics

The prevalence of IgG deficiency is not clear. Some studies estimated that the prevalence of IgG deficiency may be 1 case per 10,000 persons.Among patient populations with more frequent or severe infections, IgG subclass deficiency is a common finding. In two large series from France, IgG subclass deficiency was reported in 20 percent of 483 patients with abnormally recurrent, prolonged, or severe infection; IgG3 was the most common deficiency.^[72]^[73]

In a report of 1175 adults with symptoms suggestive of an antibody deficiency, decreased IgG1, IgG2, IgG3, and IgG4 levels were reported in 28, 17, 13, and 9 percent, respectively.^[74]

Age

IgG deficiency can affect both children and adults. The most common subclass deficiency in early childhood is IgG2 deficiency; in adults, IgG1 and IgG3 deficiencies predominate. In children, IgG1 deficiency accounts for higher cases of the total IgG deficiency in comparison to adults. even though children reach the adult levels of IgG1 and IgG3, but the development of IgG2 and IgG4 is slower. In some children, maturation of IgG subclasses may be delayed until the adolescence.^[75]

Gender

The gender prevalance of IgG deficiency differs in children and adults. In children, IgG deficiency is more common in boys by a ratio of 3:1. In contrast, there is a predominance of females after age 16. This shift in gender distribution may be owing to hormonal influences upon the immune system.^[76]

Race

There is no racial predilection for IgG deficiency.

Risk Factors

Common risk factors in the development of IgG deficiency:

Protein-losing conditions: enteropathies, nephrotic syndrome, burns, and other traumas may cause abnormal loss of immunoglobulins.
Intense exercise or excessive physical stress
Smoking
Aging

Natural History, Complications and Prognosis

Natural History

The majority of patients with IgG deficiency remain asymptomatic.^[77] In addition, there are patients with complete deficiencies of multiple combinations of IgG1, IgG2, IgG4, IgE, or IgA deficiency who remain healthy and free of infections.^[78]

Complications

Common complications of IgG deficiency include bronchiectasis, bronchiolitis obliterans , interstitial lung disease , mediastinal and/or hilar adenopathy, and malignancy.

Prognosis

Prognosis is mainly affected by the degree of deficiency as well as the age of the patient. Evidence suggests that the majority of children younger than eight years of age with IgG subclass deficiency will normalize IgG subclass level.^[5]

Adults with clinically notable IgG subclass deficiency and diminished particular antibody responses will scarcely reach previous normal level of a deficient IgG subclass.

Diagnosis

Diagnostic Criteria

IgG deficiency is a laboratory finding that may be not associated with significant clinical presentations. The diagnosis of a clinically significant IgG deficiency needs evidence of antibody dysfunction in the form of recurrent infections and an inadequate response to vaccine challenge.

The diagnosis of IgG deficiency required the following two diagnostic criteria to meet in the clinical history of recurrent sinopulmonary infections:^[79]

low IgG subclass levels
poor antibody response to the vaccine challenge

Symptoms

IgG deficiency is usually asymptomatic.
Symptoms of IgG deficiency may include the symptoms of recurrent sinopulmonary infections include otitis media, rhinosinusitis, and pneumonia or even more serious infections that can occur such as osteomyelitis, meningitis, septicemia, diarrhea, and various skin infections.^[1]

Physical Examination

Physical examination of patients with longstanding immune defects may be remarkable for:^[80]

Low body mass index
Scarring of tympanic membranes or skin
Signs of chronic lung disease such as chronic cough, absent gag reflex, clubbing, crackles, or wheezing to suggest bronchiectasis
Ongoing infection signs of chronic sinusitis, oral thrush, warts, or dermatophyte infections

Laboratory Findings

IgG deficiency is a laboratory finding that may be not associated with significant clinical presentations. The normal amounts for IgG subclasses are wide and differ with the age of the patients.

For children 4 to 10 years of age, levels below the following are considered abnormal:^[81]

IgG1 level <250 mg/dL
IgG2 level <50 mg/dL
IgG3 level <15 mg/dL
IgG4 level <1 mg/dL

For individuals older than 10 years of age, levels below the following are considered abnormal:

IgG1 level <300 mg/dL
IgG2 level <50 mg/dL
IgG3 level <25 mg/dL
IgG4 level <1 mg/dL

Vaccine Challenge Response

IgG subclass deficiency is a laboratory finding which does not necessarily cause clinical presentations. For final diagnosis of IgG subclass deficiency, patients must be evaluated for antibody dysfunction in both polysaccharides and proteins antigens. The function can be assessed by measuring antibody titers to previously administered vaccines or natural infections. If titers are not in the protective range, a vaccine challenge should be performed with the administration of vaccines with measurement of pre- and postimmunization titers

Titers of IgG antibodies to tetanus and diphtheria in vaccinated children and adults are used to evaluate immune responsiveness to protein antigens. Results are reported as IgG in general, although the antibody responses generated by these vaccines are largely (but not exclusively) composed of IgG1 and IgG3 antibodies, which is sometimes important in the evaluation of IgG subclass deficiency.^[82]

Interpretation of Hib titers — The capsular polysaccharide polyribosylribitol phosphate (PRP) is an important antigen in immunity to Haemophilus influenzae type B (Hib). Anti-PRP IgG titers ≥1 mcg/mL are considered protective [28]. Although the polysaccharide PRP is the primary antigen, the conjugate vaccines employ either diphtheria toxoid or the outer membrane protein complex of meningococcus as the immunogenic protein. Therefore, antibodies to the Hib capsular polysaccharide in patients who received the conjugated Hib vaccine reflect a protein response, and protective antibodies against the PRP polysaccharide do not exclude unresponsiveness to the pure pneumococcal polysaccharides. Children in the United States have been receiving conjugated vaccines for prophylaxis against Hib since the early 1990s.

Treatment

Medical Therapy

The mainstay of therapy for IgG deficiency includes the following :

Immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines^[83]

Aggressive management of asthma, allergic rhinitis predisposing to recurrent sinopulmonary infections

Recognition and treatment of sinopulmonary bacterial infections since infections are less likely to clear spontaneously in patients with antibody defects.
Prophylactic antibiotics for patients with recurrent sinopulmonary infections. Evidence in support of this approach is largely derived from benefits observed in retrospective studies of children with this and similar antibody deficiencies.^[5]

Intravenous or subcutaneous immune globulin replacement is indicated if the use of prophylactic antibiotics does not cause fewer infections or in patients with persistent and symptomatic chronic rhinosinusitis. This therapy should be reserved for patients with clearly impaired responses to protein and/or polysaccharide antigens.
Intravenous immune globulin therapy, at a standard dose range of 400 to 600 mg/kg, can be infused every three to four weeks.^[6] Immune globulin can also be replaced subcutaneously at weekly intervals.
Immune globulin therapy should be administered for one to two years initially, at which point the patient's status should be re-evaluated to determine if the number and/or severity of infections have been reduced. Not all patients with IgG subclass deficiencies benefit from immune globulin replacement, and the therapy should be discontinued if not effective in that individual.^[84]

Prevention

There are no primary preventive measures available for IgG deficiency.

Secondary and tertiary prevention strategies following IgG deficiency include avoidance measures, vaccination, prophylactic antibiotics, immune globulin therapy,and when infections do occur, broader spectrum and more prolonged antibiotics are often recommended.
Avoidance: to reduce exposure to others with potentially contagious illnesses: proper handwashing and use of alcohol-based disinfectants should be provided to patients and their families; Co-sleeping among family members should be minimized, and immunization of family members and close contacts
Careful attention should be paid to patient's oral hygiene and dental health.
Vaccination Immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines Advisory Committee on Immunization Practices (ACIP)^[85]
Recommended that conjugated Hib vaccine be administered in patients with IgG2 subclass deficiency and those with specific antibody deficiency (SAD) ^[86]^[87]
Antimicrobial therapy: Treating acute infections and prophylactic antimicrobial therapy among patients with recurrent sinopulmonary infections or ongoing lung disease is helpful. Thus, immediate recognition and treatment with antibiotics can help prevent chronic infections and infectious complications. It is important to ensure that the infection has treated completely at the end of a course of antibiotics, as patients with immunodeficiency sometimes necessitate longer durations of therapy. Antibiotic resistance does not seem to be a serious problem in patients with primary immunodeficiency, for causes which are not clearly understood, then the same antibiotics continue to be useful, regardless of prolonged or frequent exposure.^[88]

References

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↑ T. Zenone, P. J. Souquet, C. Cunningham-Rundles & J. P. Bernard (1996). "Hodgkin's disease associated with IgA and IgG subclass deficiency". Journal of internal medicine. 240 (2): 99–102. PMID 8810936. Unknown parameter |month= ignored (help)
↑ W. B. Klaustermeyer, M. E. Gianos, M. L. Kurohara, H. T. Dao & D. C. Heiner (1992). "IgG subclass deficiency associated with corticosteroids in obstructive lung disease". Chest. 102 (4): 1137–1142. PMID 1343817. Unknown parameter |month= ignored (help)
↑ I. Qvarfordt, G. C. Riise, B. A. Andersson & S. Larsson (2001). "IgG subclasses in smokers with chronic bronchitis and recurrent exacerbations". Thorax. 56 (6): 445–449. PMID 11359959. Unknown parameter |month= ignored (help)
↑ P. Aucouturier, C. Lacombe, C. Bremard, Y. Lebranchu, M. Seligmann, C. Griscelli & J. L. Preud'Homme (1989). "Serum IgG subclass levels in patients with primary immunodeficiency syndromes or abnormal susceptibility to infections". Clinical immunology and immunopathology. 51 (1): 22–37. PMID 2924438. Unknown parameter |month= ignored (help)
↑ P. Aucouturier, M. Mariault, C. Lacombe & J. L. Preud'homme (1992). "Frequency of selective IgG subclass deficiency: a reappraisal". Clinical immunology and immunopathology. 63 (3): 289–291. PMID 1623649. Unknown parameter |month= ignored (help)
↑ Meulenbroek AJ, Zeijlemaker WP. Human IgG subclasses: Useful diagnostic markers for immunocompetence, 2nd edition, CLB, Amsterdam, The Netherlands 2000
↑ F. C. 3rd Javier, C. M. Moore & R. U. Sorensen (2000). "Distribution of primary immunodeficiency diseases diagnosed in a pediatric tertiary hospital". Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 84 (1): 25–30. doi:10.1016/S1081-1206(10)62736-6. PMID 10674561. Unknown parameter |month= ignored (help)
↑ L. A. Hanson, R. Soderstrom, A. Avanzini, U. Bengtsson, J. Bjorkander & T. Soderstrom (1988). "Immunoglobulin subclass deficiency". The Pediatric infectious disease journal. 7 (5 Suppl): S17–S21. PMID 3041356. Unknown parameter |month= ignored (help)
↑ P. G. Shackelford, D. M. Granoff, J. V. Madassery, M. G. Scott & M. H. Nahm (1990). "Clinical and immunologic characteristics of healthy children with subnormal serum concentrations of IgG2". Pediatric research. 27 (1): 16–21. doi:10.1203/00006450-199001000-00004. PMID 2296465. Unknown parameter |month= ignored (help)
↑ M. P. Lefranc, L. Hammarstrom, C. I. Smith & G. Lefranc (1991). "Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis". Immunodeficiency reviews. 2 (4): 265–281. PMID 1905558.
↑ Francisco A. Bonilla, David A. Khan, Zuhair K. Ballas, Javier Chinen, Michael M. Frank, Joyce T. Hsu, Michael Keller, Lisa J. Kobrynski, Hirsh D. Komarow, Bruce Mazer, Robert P. Jr Nelson, Jordan S. Orange, John M. Routes, William T. Shearer, Ricardo U. Sorensen, James W. Verbsky, David I. Bernstein, Joann Blessing-Moore, David Lang, Richard A. Nicklas, John Oppenheimer, Jay M. Portnoy, Christopher R. Randolph, Diane Schuller, Sheldon L. Spector, Stephen Tilles & Dana Wallace (2015). "Practice parameter for the diagnosis and management of primary immunodeficiency". The Journal of allergy and clinical immunology. 136 (5): 1186–1205. doi:10.1016/j.jaci.2015.04.049. PMID 26371839. Unknown parameter |month= ignored (help)
↑ F. S. Rosen, M. D. Cooper & R. J. Wedgwood (1995). "The primary immunodeficiencies". The New England journal of medicine. 333 (7): 431–440. doi:10.1056/NEJM199508173330707. PMID 7616993. Unknown parameter |month= ignored (help)
↑ L. A. Hanson, R. Soderstrom, A. Avanzini, U. Bengtsson, J. Bjorkander & T. Soderstrom (1988). "Immunoglobulin subclass deficiency". The Pediatric infectious disease journal. 7 (5 Suppl): S17–S21. PMID 3041356. Unknown parameter |month= ignored (help)
↑ Jordan S. Orange, Mark Ballow, E. Richard Stiehm, Zuhair K. Ballas, Javier Chinen, Maite De La Morena, Dinakantha Kumararatne, Terry O. Harville, Paul Hesterberg, Majed Koleilat, Sean McGhee, Elena E. Perez, Jason Raasch, Rebecca Scherzer, Harry Schroeder, Christine Seroogy, Aarnoud Huissoon, Ricardo U. Sorensen & Rohit Katial (2012). "Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology". The Journal of allergy and clinical immunology. 130 (3 Suppl): S1–24. doi:10.1016/j.jaci.2012.07.002. PMID 22935624. Unknown parameter |month= ignored (help)
↑ R. U. Sorensen, L. E. Leiva, P. A. Giangrosso, B. Butler, F. C. 3rd Javier, D. M. Sacerdote, N. Bradford & C. Moore (1998). "Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine". The Pediatric infectious disease journal. 17 (8): 685–691. PMID 9726341. Unknown parameter |month= ignored (help)
↑ Ann-Margreth Olinder-Nielsen, Carl Granert, Pia Forsberg, Vanda Friman, Auli Vietorisz & Janne Bjorkander (2007). "Immunoglobulin prophylaxis in 350 adults with IgG subclass deficiency and recurrent respiratory tract infections: a long-term follow-up". Scandinavian journal of infectious diseases. 39 (1): 44–50. doi:10.1080/00365540600951192. PMID 17366012.
↑ R. U. Sorensen, L. E. Leiva, P. A. Giangrosso, B. Butler, F. C. 3rd Javier, D. M. Sacerdote, N. Bradford & C. Moore (1998). "Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine". The Pediatric infectious disease journal. 17 (8): 685–691. PMID 9726341. Unknown parameter |month= ignored (help)
↑ R. U. Sorensen, L. E. Leiva, P. A. Giangrosso, B. Butler, F. C. 3rd Javier, D. M. Sacerdote, N. Bradford & C. Moore (1998). "Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine". The Pediatric infectious disease journal. 17 (8): 685–691. PMID 9726341. Unknown parameter |month= ignored (help)
↑ Lorry G. Rubin, Myron J. Levin, Per Ljungman, E. Graham Davies, Robin Avery, Marcie Tomblyn, Athos Bousvaros, Shireesha Dhanireddy, Lillian Sung, Harry Keyserling & Insoo Kang (2014). "2013 IDSA clinical practice guideline for vaccination of the immunocompromised host". Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 58 (3): e44–100. doi:10.1093/cid/cit684. PMID 24311479. Unknown parameter |month= ignored (help)
↑ A. Samuelson, S. Borrelli, R. Gustafson, L. Hammarstrom, C. I. Smith, J. Jonasson & A. A. Lindberg (1995). "Characterization of Haemophilus influenzae isolates from the respiratory tract of patients with primary antibody deficiencies: evidence for persistent colonizations". Scandinavian journal of infectious diseases. 27 (4): 303–313. PMID 8658061.

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v t e Immune disorders: Immunodeficiency (D80-D85, 279)
Primary	Template:Navbox subgroup
Acquired	AIDS
See also hematological malignancy and hematology

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{SI}}
-{{CMG}}{{AE}}{{M.B}}
+{{CMG}}{{AE}}{{M.B}} {{HK}}
 ==Overview==
-'''IgG deficiency''' ('''Selective deficiency of immunoglobulin G''') is a form of [[hypogammaglobulinemia]] where the proportional levels of the [[IgG]] isotype are reduced relative to other [[immunoglobulin]] isotypes. IgG deficiency is often found in children as transient hypogammaglobulinemia of infancy (THI), which may occur with or without additional decreases in [[IgA]] or [[IgM]].
+IgG deficiency is a form of [[hypogammaglobulinemia]] where the serum concentrations of one or more subclasses of [[IgG]] are diminished relative to other [[immunoglobulin]] isotypes, meanwhile total IgG concentration is noral. IgG deficiency is a laboratory finding that may be not associated with significant clinical presentations. The diagnosis of a clinically significant IgG deficiency needs evidence of antibody dysfunction in the form of recurrent infections and an inadequate response to vaccine challenge.
-IgG has four subclasses: IgG<sub>1</sub>, IgG<sub>2</sub>, IgG<sub>3</sub>, and IgG<sub>4</sub>. It is possible to have either a global IgG deficiency, or a deficiency of one or more specific subclasses of IgG.<ref name="pmid12803653">{{cite journal |vauthors=Barton JC, Bertoli LF, Acton RT |title=HLA-A and -B alleles and haplotypes in 240 index patients with common variable immunodeficiency and selective IgG subclass deficiency in central Alabama |journal=BMC Med. Genet. |volume=4|pages=3 |date=June 2003 |pmid=12803653 |pmc=166147 |doi=10.1186/1471-2350-4-3 |url=http://www.biomedcentral.com/1471-2350/4/3}}</ref><ref name="pmid12049826">{{cite journal |vauthors=Dhooge IJ, van Kempen MJ, Sanders LA, Rijkers GT |title=Deficient IgA and IgG2 anti-pneumococcal antibody levels and response to vaccination in otitis prone children |journal=Int. J. Pediatr. Otorhinolaryngol. |volume=64 |issue=2 |pages=133–41 |date=June 2002 |pmid=12049826 |doi= 10.1016/S0165-5876(02)00068-X|url=http://linkinghub.elsevier.com/retrieve/pii/S016558760200068X}}</ref> The main clinically relevant form of IgG deficiency is IgG<sub>2</sub>. IgG<sub>3</sub> deficiency is not usually encountered without other concomitant immunoglobulin deficiencies, and IgG<sub>4</sub> deficiency is very common but usually asymptomatic.<ref>{{cite journal|last1=Driessen|first1=G|last2=van der Burg|first2=M|title=Educational paper: primary antibody deficiencies.|journal=European journal of pediatrics|date=June 2011|volume=170|issue=6|pages=693–702|pmid=21544519|doi=10.1007/s00431-011-1474-x}}</ref>
+Most patients with IgG deficiency are usually asymptomatic. Symptoms of  IgG deficiency may include the symptoms of recurrent sinopulmonary infections include otitis media, rhinosinusitis, and pneumonia or even more serious infections that can occur such as osteomyelitis, meningitis, septicemia, diarrhea, and skin infections.<ref name=":0" />
-IgG1 is present in the bloodstream at a percentage of about 60-70%, IgG2-20-30%, IgG3 about 5-8 %, and IgG4 1-3 %. IgG subclass deficiencies affect only IgG subclasses (usually IgG2 or IgG3), with normal total IgG and IgM immunoglobulins and other components of the immune system being at normal levels. These deficiencies can affect only one subclass or involve an association of two subclasses, such as IgG2 and IgG4. IgG deficiencies are usually not diagnosed until the age of 10. Some of the IgG levels in the blood are undetectable and have a low percentage such as IgG4, which makes it hard to dertermine if a deficiency is actually present. IgG subclass deficiencies are sometimes correlated with bad responses to pneumoccal polyscaccharides, especially IgG2 and or IgG4 deficiency. Some of these deficiencies are also involved with [[Autoimmune pancreatitis|pancreatitis]] and have been linked to IgG4 levels.
+IgG has four subclasses: IgG<sub>1</sub>, IgG<sub>2</sub>, IgG<sub>3</sub>, and IgG<sub>4</sub>. It is possible to have either a global IgG deficiency, or a deficiency of one or more specific subclasses of IgG.<ref name="pmid12803653">{{cite journal |vauthors=Barton JC, Bertoli LF, Acton RT |title=HLA-A and -B alleles and haplotypes in 240 index patients with common variable immunodeficiency and selective IgG subclass deficiency in central Alabama |journal=BMC Med. Genet. |volume=4|pages=3 |date=June 2003 |pmid=12803653 |pmc=166147 |doi=10.1186/1471-2350-4-3 |url=http://www.biomedcentral.com/1471-2350/4/3}}</ref><ref name="pmid12049826">{{cite journal |vauthors=Dhooge IJ, van Kempen MJ, Sanders LA, Rijkers GT |title=Deficient IgA and IgG2 anti-pneumococcal antibody levels and response to vaccination in otitis prone children |journal=Int. J. Pediatr. Otorhinolaryngol. |volume=64 |issue=2 |pages=133–41 |date=June 2002 |pmid=12049826 |doi= 10.1016/S0165-5876(02)00068-X|url=http://linkinghub.elsevier.com/retrieve/pii/S016558760200068X}}</ref>  Since IgG1 forms about 70 percent of total IgG patients with  IgG1 deficiency are classified as [[Common variable immunodeficiency|common variable immunodeficiency (CVID),]] a diagnosis that also needs reduced levels of [[Immunoglobulin A|IgA]] and/or [[Immunoglobulin M|IgM]].
+IgG2 subclass deficiency is the main clinically relevant form of IgG deficiency  and is more prevalent among children than adults and is one of the most frequently identified disorders in children with recurrent infections in children or may present as [[transient hypogammaglobulinemia of infancy]] (THI), and may occur with or without additional reduction in [[IgA]] or [[IgM]]. IgG<sub>3</sub> deficiency is not usually encountered without other concomitant immunoglobulin deficiencies, and IgG<sub>4</sub> deficiency is very common but usually asymptomatic.<ref>{{cite journal|last1=Driessen|first1=G|last2=van der Burg|first2=M|title=Educational paper: primary antibody deficiencies.|journal=European journal of pediatrics|date=June 2011|volume=170|issue=6|pages=693–702|pmid=21544519|doi=10.1007/s00431-011-1474-x}}</ref>
+The diagnosis of a clinically significant IgG deficiency needs evidence of antibody dysfunction in the form of recurrent infections and an inadequate response to vaccine challenge. Management consists of immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines, aggressive treatment of other conditions predisposing to recurrent sinopulmonary infections and appropriate antibiotic therapy for infections and the use of prophylactic antibiotics for patients with repeated [[Rhinosinusitis|sinopulmonary infections]].<ref name="WolpertKnutsen1998" />
+[[Intravenous therapy|Intravenous]] or subcutaneous immune globulin replacement should be reserved for patients with clearly impaired responses to protein and/or polysaccharide [[Antigen|antigens]] and/or if the use of prophylactic antibiotics does not cause fewer infections or in patients with persistent and symptomatic chronic [[rhinosinusitis]] .<ref name=":1" />
 ==Historical Perspective==
-In 1952, Bruton reported a condition in an 8-year-old boy with recurrent episodes of bacterial infections and sepsis with the same serotypes of pneumococcus, while he had intact lymphoid tissue and B-cells but had decreased IgG levels and he had no antibodies against this pathogen.<ref name="MelamedHeffron2015">{{cite journal|last1=Melamed|first1=Isaac R.|last2=Heffron|first2=Melinda|last3=McGee|first3=Sean|last4=Ulltate Sanz|first4=Laura|last5=Testori|first5=Alessandro|title=A new subset of common variable immune deficiency characterized by reduced C1 esterase inhibitor levels|journal=Annals of Allergy, Asthma & Immunology|volume=115|issue=1|year=2015|pages=83–84|issn=10811206|doi=10.1016/j.anai.2015.04.023}}</ref>
+In 1952, Bruton reported a condition in an 8-year-old boy with recurrent episodes of bacterial infections and [[sepsis]] with the same [[serotypes]] of pneumococcus, while he had intact lymphoid tissue and [[B cell|B-cells]] but had decreased IgG levels and he had no [[antibodies]] against this pathogen.<ref name="MelamedHeffron2015">{{cite journal|last1=Melamed|first1=Isaac R.|last2=Heffron|first2=Melinda|last3=McGee|first3=Sean|last4=Ulltate Sanz|first4=Laura|last5=Testori|first5=Alessandro|title=A new subset of common variable immune deficiency characterized by reduced C1 esterase inhibitor levels|journal=Annals of Allergy, Asthma & Immunology|volume=115|issue=1|year=2015|pages=83–84|issn=10811206|doi=10.1016/j.anai.2015.04.023}}</ref>
 In the 1960s, by the discovery of the IgG subclasses, further aspects of IgG deficiency and recurrent infection, were uncovered. and thrown new light on the understanding of  IgG deficiencies subclasses, as isolated deficiencies (eg, selective IgG deficiency) or in association with deficiencies of other immunoglobulin types. Moreover, how even if the total IgG concentration is normal, deficiencies of one or more individual IgG subclasses, may be observed.<ref name="VidarssonDekkers2014">{{cite journal|last1=Vidarsson|first1=Gestur|last2=Dekkers|first2=Gillian|last3=Rispens|first3=Theo|title=IgG Subclasses and Allotypes: From Structure to Effector Functions|journal=Frontiers in Immunology|volume=5|year=2014|issn=1664-3224|doi=10.3389/fimmu.2014.00520}}</ref>
@@ Line 17: / Line 23: @@
 ==Classification==
 IgG deficiency may be classified according to  individual IgG subclasses deficiency into four subtypes:
-:*'''IgG1 deficiency :''' since IgG1 normally comprises almost two-thirds of the total serum IgG Most patients with IgG1 deficiency have generalized hypogammaglobulinemia.Thus, most patients with significant IgG1 deficiency are classified as common variable immunodeficiency (CVID), a diagnosis that also requires decreased levels of IgA and/or IgM. Only patients with selective IgG1 deficiency and normal levels of total IgG should be diagnosed with IgG1 deficiency. Selective IgG1 deficiency with normal total IgG is uncommon.<ref>{{Cite journal
+:*'''IgG1 deficiency :''' since IgG1 normally comprises almost two-thirds of the total serum IgG most patients with IgG1 deficiency have generalized [[hypogammaglobulinemia]].Thus, most patients with significant IgG1 deficiency are classified as [[Common variable immunodeficiency|common variable immunodeficiency (CVID)]], a diagnosis that also requires decreased levels of [[Immunoglobulin A|IgA]] and/or [[Immunoglobulin M|IgM]]. Only patients with selective IgG1 deficiency and normal levels of total IgG should be diagnosed with IgG1 deficiency. Selective IgG1 deficiency with normal total IgG is uncommon.<ref>{{Cite journal
   | author = [[C. Lacombe]], [[P. Aucouturier]] & [[J. L. Preud'homme]]
   | title = Selective IgG1 deficiency
@@ Line 85: / Line 91: @@
 ==Pathophysiology==
-Immunodeficiency diseases are described according to involvement one or more of the 4 major components of the immune system. These components are 1) B cells; 2) T cells, 3) phagocytes; and 4) complement
+Immunodeficiency diseases are described according to involvement one or more of the 4 major components of the [[immune system]].
+These components are:
+#[[B cell|B cells]]
+#[[T cell|T cells]]
+#[[Phagocyte|phagocytes]]
+#[[complement]]
-B-cell or humoral immunity is mediated by the immunoglobulins. There are five types or classes of immunoglobulin: IgG, IgA, IgM, IgD, and IgE. The IgG class of antibodies is composed of four different subtypes of IgG molecules called the IgG subclasses. These are designated IgG1, IgG2, IgG3, and IgG4. The term "IgG subclass deficiency" refers to a significant decrease in the serum concentrations of one or more subclasses of IgG in a patient whose total IgG concentration is normal <ref>Herrod HG. Clinical significance of IgG subclasses. Curr Opin Pediatr 1993; 5:696</ref>
+[[B cell|B-cell]] or [[humoral immunity]] is mediated by the [[immunoglobulins]]. There are five types or classes of immunoglobulin: [[Immunoglobulin G|IgG]], [[Immunoglobulin A|IgA]], [[Immunoglobulin M|IgM]], [[Immunoglobulin D|IgD]], and [[Immunoglobulin E|IgE]]. The IgG class of [[antibodies]] is composed of four different subtypes of IgG molecules called the IgG subclasses. These are designated IgG1, IgG2, IgG3, and IgG4. The term "IgG subclass deficiency" refers to a significant decrease in the serum concentrations of one or more subclasses of IgG in a patient whose total IgG concentration is normal <ref>Herrod HG. Clinical significance of IgG subclasses. Curr Opin Pediatr 1993; 5:696</ref>
-'''PATHOGENESIS'''
+===PATHOGENESIS===
-The primary mechanisms underlying IgG subclass deficiency are unclear. Gene deletions, transcription errors, cytokine dysregulation, immunosuppressive therapy, and allotypic variations are some mechanisms that have been described:
+The primary mechanisms underlying IgG subclass deficiency are unclear. [[Deletion (genetics)|Gene deletions]], [[Transcription (genetics)|transcription errors]], [[Cytokines and their receptors|cytokine dysregulation]], [[Immunosuppressive agents|immunosuppressive therapy]], and allotypic variations are some mechanisms that have been described ''':'''
-* '''Gene deletions:''' Heterozygous gene deletions cause the reduction in the serum concentration of the corresponding subclass. Deletions have been detected for genes ''C-gamma-1'', ''C-gamma-2'', and ''C-gamma-4'' . Homozygous deletions of large portions of the immunoglobulin heavy chain gene, causes the absence of multiple immunoglobulin classes, and are also described. Such patients may have no detectable IgG1, IgG2, IgG4, IgA1, or IgE .<ref>{{Cite journal
+* '''Gene deletions:''' Heterozygous [[Deletion (genetics)|gene deletions]] cause the reduction in the serum concentration of the corresponding subclass. Deletions have been detected for genes ''C-gamma-1'', ''C-gamma-2'', and ''C-gamma-4'' . Homozygous deletions of large portions of the immunoglobulin heavy chain gene, causes the absence of multiple immunoglobulin classes, and are also described. Such patients may have no detectable IgG1, IgG2, IgG4, IgA1, or IgE .<ref>{{Cite journal
   | author = [[H. Rabbani]], [[N. Kondo]], [[C. I. Smith]] & [[L. Hammarstrom]]
   | title = The influence of gene deletions and duplications within the IGHC locus on serum immunoglobulin subclass levels
@@ Line 103: / Line 114: @@
   | pmid = 7554471
 }}</ref>
-* '''Transcription errors:''' Changes of germline transcription and limitation fragment length polymorphisms 5' of the S-gamma-4 loci within the gamma-chain constant region gene complex have been described among patients with IgG4 deficiency  compared with controls.<ref>{{Cite journal
+* '''Transcription errors:''' Changes of [[Transcription (genetics)|germline transcription]] and limitation fragment length [[polymorphisms]] 5' of the S-gamma-4 [[Locus (genetics)|loci]] within the gamma-chain constant region gene complex have been described among patients with IgG4 deficiency  compared with controls.<ref>{{Cite journal
   | author = [[A. Bottaro]], [[M. DeMarchi]], [[G. G. DeLange]], [[C. Boccazzi]], [[L. Fubini]], [[C. Borra]], [[N. Cappello]] & [[A. O. Carbonara]]
   | title = Human IGHC locus restriction fragment length polymorphisms in IgG4 deficiency: evidence for a structural IGHC defect
@@ Line 132: / Line 143: @@
 ==Differentiating IgG deficiency from other Diseases==
-IgG deficiency must be differentiated from other diseases that cause recurrent episodic infections, especially recurrent sinopulmonary infections include otitis media, rhinosinusitis, and pneumonia. Besides serious infections such as osteomyelitis, meningitis, septicemia, diarrhea, and various skin infections, are conditions propose the possibility for immunodeficiency:
+IgG deficiency must be differentiated from other diseases that cause recurrent episodic [[infections]], especially recurrent sinopulmonary infections including [[otitis media]], [[rhinosinusitis]], and [[pneumonia]]. IgG defieciency should be differentiated from other disorders leading to [[hypogammaglobulinemia]] and defects of [[humoral immunity]]. The following conditions may be considered as differentials:<ref name="pmid17910333">{{cite journal |vauthors=Agarwal S, Cunningham-Rundles C |title=Assessment and clinical interpretation of reduced IgG values |journal=Ann. 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What is evident? |journal=Neuropediatrics |volume=43 |issue=3 |pages=119–29 |date=June 2012 |pmid=22614068 |doi=10.1055/s-0032-1313915 |url=}}</ref><ref name="pmid13542097">{{cite journal |vauthors=BODER E, SEDGWICK RP |title=Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection |journal=Pediatrics |volume=21 |issue=4 |pages=526–54 |date=April 1958 |pmid=13542097 |doi= |url=}}</ref><ref name="pmid24683014">{{cite journal |vauthors=Sahama I, Sinclair K, Pannek K, Lavin M, Rose S |title=Radiological imaging in ataxia telangiectasia: a review |journal=Cerebellum |volume=13 |issue=4 |pages=521–30 |date=August 2014 |pmid=24683014 |doi=10.1007/s12311-014-0557-4 |url=}}</ref><ref name="pmid23886747">{{cite journal |vauthors=Lin DD, Barker PB, Lederman HM, Crawford TO |title=Cerebral abnormalities in adults with ataxia-telangiectasia |journal=AJNR Am J Neuroradiol |volume=35 |issue=1 |pages=119–23 |date=January 2014 |pmid=23886747 |pmc=4106125 |doi=10.3174/ajnr.A3646 |url=}}</ref><ref name="pmid15069401">{{cite journal |vauthors=Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM |title=Immunodeficiency and infections in ataxia-telangiectasia |journal=J. Pediatr. |volume=144 |issue=4 |pages=505–11 |date=April 2004 |pmid=15069401 |doi=10.1016/j.jpeds.2003.12.046 |url=}}</ref>
+{| class="wikitable"
+|+
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disorder
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Defect (Mechanism of Development)
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Characteristic Features
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Clinical Presentation
+! align="center" style="background:#4479BA; color: #FFFFFF;" + |Laboratory Findings
+|-
+|[[X-linked agammaglobulinemia|'''X-Linked (Bruton) Agammaglobulinemia''']]
+|
+* Defect in [[tyrosine kinase]] [[gene]] ([[Bruton's tyrosine kinase|BTK]])
+* [[B cells]] fail to mature
+|
+* [[X-linked recessive]] pattern of inheritance
+* Increased [[prevalence]] in [[males]]
+|
+* Recurrent [[bacterial]] and [[enteroviral]] [[infections]] after 6 months of age
+* Pre-disposition to development of [[infections]] by [[encapsulated organisms]]
+* Pre-disposition to development of Giardia infections
+* Absent lymph nodes and tonsils
+|
+* Normal [[CD19|CD19+ B cell]] count
+* Decreased pro-[[B cells]]
+* Increased pre-[[B cells]]
+* Decreased [[immunoglobulins]] of all classes
+|-
+|[[IgA deficiency|'''Selective IgA Deficiency''']]
+|
+* [[Stem cell]] defect (Transferrable with [[Bone marrow transplant|marrow transplant]])
+* Lack of [[Interleukin 4|IL-4]], [[Interleukin 6|IL-6]], [[Interleukin 7|IL-7]], [[Interleukin 10|IL-10]], [[TGF beta|TGF-β]], and [[Interleukin 21|IL-21]]
+* [[Mutations]] in [[transmembrane]] activator and calcium-modulator and [[cyclophilin]] ligand interactor ([[TACI]], [[TNFRSF13B]])
+|
+* Most common primary [[immune deficiency]]
+|
+* Majority of the cases are [[asymptomatic]]
+* Respiratory and [[gastrointestinal]] infections ([[mucosal]] infections)
+* Associated with [[autoimmune diseases]]
+* [[Atopy]]
+* [[Anaphylaxis]] to [[IgA]] containing products
+|
+* Serum [[IgA]] < 7 mg/dl
+* Normal [[IgG]] and [[IgM]] levels
+|-
+|[[Common variable immunodeficiency|'''Common Variable Immunodeficiency''']]
+|
+* Defective [[B cell]] differentiation
+|
+* May be acquired in 20-30 years of age
+|
+* May present with other [[autoimmune diseases]]
+* Associated with [[bronchiectasis]]
+* Associated with [[lymphoma]]
+* Associated with sinopulmonary infections ([[Bacterial]], [[enteroviral]] and [[parasitic]] such as [[Giardia]])
+|
+* Decreased [[plasma cells]]
+* Decreased [[immunoglobulins]]
+|-
+|[[Job's syndrome|'''Autosomal dominant hyper IgE syndrome (Job's Syndrome)''']]
+|
+* Defieciency of [[T helper 17 cell|Th17 cells]] due to [[STAT3]] [[mutation]]
+* Impaired [[neutrophils]] to sites of [[infection]]
+|
+* Distinctive coarse facies
+* Cold (non-inflammatory) Staphylococcal abscesses
+* Retained primary teeth
+* Eczema
+|
+|
+* Increased levels of [[IgE]]
+* Decreased levels of [[interferon gamma]] (IFN-gamma)
+|-
+|[[Severe combined immunodeficiency|'''Severe combined immunodeficiency (SCID)''']]
+|
+* Defective [[Interleukin-2 receptor|interleukin-2 receptor gamma chain]]
+* [[Adenosine deaminase]] deficiency
+* Reg 1 and Reg 2 [[nonsense mutations]]
+|
+* [[Interleukin 20 receptor, alpha subunit|IL-2R]] disease is [[X-linked]]
+* [[Adenosine deaminase|ADA]] deficiency and reg mutations are typically [[autosomal recessive]]
+|
+* [[Failure to thrive]]
+* [[Chronic diarrhea]]
+* [[Thrush]]
+* Recurrent [[bacterial]], [[viral]] and [[protozoal]] infections
+* Treatment is [[bone marrow]] [[transplant]]
+|
+* Decreased [[T cell]] receptor excision circles (TRECs)
+* Abscence of [[thymic]] shadow on [[Chest X-ray|chest X-Ray]]
+* Absent [[germinal centers]] of [[lymph node biopsy]]
+* Absent [[T cells]] on [[flow cytometry]]
+|-
+|[[Ataxia telangiectasia|'''Ataxia Telangiectasia''']]
+|
+* Defect in [[ATM|ATM gene]]
+* [[DNA]] double stranded breaks leading to [[cell cycle]] arrest
+|
+* Hypersensitivity to [[X-Ray|X-Rays]]
+|
+* Triad of:
+** [[Ataxia]]
+** Spider [[Angioma|angiomas]] (Nests of distended [[capillaries]])
+** [[IgA deficiency]]
+|
+* Increased [[alpha fetoprotein]] ([[Alpha-fetoprotein|AFP]])
+* Decreased [[IgA]], [[IgG]] and [[IgE]]
+* [[Lymphopenia]]
+* [[Cerebellar]] atrophy
+|-
+|[[Hyper IgM Syndrome Type 1|'''Hyper IgM Syndrome''']]
+|
+* Defective [[CD40L]] ([[CD40L|CD40 ligand]]) on [[T helper cell|Th cells]] leading to [[class switching]] defect
+|
+* [[X-linked recessive]] pattern of inheritance
+|
+* Severe pyogenic infections in early life
+* Opportunistic infection with:
+** [[Pneumocystis jiroveci]]
+** [[Cryptosporidium]]
+** [[Cytomegalovirus]] ([[Cytomegalovirus infection|CMV]])
+|
+* Increased [[Immunoglobulin M|IgM]]
+* Decreased [[Immunoglobulin G|IgG]], [[IgA]] and [[Immunoglobulin E|IgE]]
+* No [[germinal centers]]
+|-
+|[[Wiskott-Aldrich syndrome|'''Wiskott-Aldrich Syndrome''']]
+|
+* [[Mutation]] in [[WAS]] [[gene]]
+* [[T cells]] unable to reorganize [[actin]] [[microfilaments]] ([[microfilament]] defect)
+|
+* [[X-linked recessive]] pattern of inheritance
+* Increased risk of [[autoimmune disease]] and [[malignancy]]
+|
+* [[Thrombocytopenic purpura]]
+* [[Eczema]]
+* Recurrent [[infections]]
+|
+* Decreased to normal [[Immunoglobulin G|IgG]] and [[Immunoglobulin M|IgM]]
+* Increased [[Immunoglobulin E|IgE]] and [[IgA]]
+* Fewer and smaller [[platelets]]
+|}
 :*Malignancy: can cause the reduction in the immunoglobulin production.<ref>{{Cite journal
   | author = [[T. Zenone]], [[P. J. Souquet]], [[C. Cunningham-Rundles]] & [[J. P. Bernard]]
@@ Line 144: / Line 295: @@
   | pmid = 8810936
 }}</ref>
-*Viral infections: such as Epstein-Barr virus, HIV, cytomegalovirus are other causes of hypogammaglobulinemia..
+*Viral infections: such as Epstein-Barr virus, HIV, cytomegalovirus are other causes of hypogammaglobulinemia.
 *Side effect of certain medications: Some drugs include systemic glucocorticoids, phenytoin, and carbamazepine, have been associated with IgG deficiency.<ref>{{Cite journal
   | author = [[W. B. Klaustermeyer]], [[M. E. Gianos]], [[M. L. Kurohara]], [[H. T. Dao]] & [[D. C. Heiner]]
@@ Line 169: / Line 320: @@
 }}</ref>
 *Protein-losing conditions: enteropathies, nephrotic syndrome, burns, and other traumas may cause abnormal loss of immunoglobulins.
 ==Epidemiology and Demographics==
 The prevalence of  IgG deficiency is not clear. Some studies estimated that the prevalence of IgG deficiency may be 1 case per 10,000 persons.Among patient populations with more frequent or severe infections, IgG subclass deficiency is a common finding. In two large series from France, IgG subclass deficiency was reported in 20 percent of 483 patients with abnormally recurrent, prolonged, or severe infection; IgG3 was the most common deficiency.<ref>{{Cite journal
@@ Line 225: / Line 377: @@
 ==Risk Factors==
-Common risk factors in the development of IgG deficiency:
+Common risk factors in the development of IgG deficiency''':'''
 *Protein-losing conditions: enteropathies, nephrotic syndrome, burns, and other traumas may cause abnormal loss of immunoglobulins.
-*''Intense exercise or excessive physical stress''
+*Intense exercise or excessive physical stress
-*''Smoking''
+*Smoking
-*''Aging''
+*Aging
 == Natural History, Complications and Prognosis==
+'''Natural History'''
 *The majority of patients with IgG deficiency remain asymptomatic.<ref>{{Cite journal
   | author = [[P. G. Shackelford]], [[D. M. Granoff]], [[J. V. Madassery]], [[M. G. Scott]] & [[M. H. Nahm]]
@@ Line 254: / Line 407: @@
   | pmid = 1905558
 }}</ref>
-*Early clinical features include recurrent sinopulmonary infections.  More serious infections that can occur include osteomyelitis, meningitis, septicemia, diarrhea, and various skin infections
+'''Complications'''
-*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
+*Common complications of IgG deficiency include bronchiectasis, bronchiolitis obliterans , interstitial lung disease , mediastinal and/or hilar adenopathy, and malignancy.
-*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
+'''Prognosis'''
-*Prognosis is generally influenced by the age of the patient as well as the degree of deficiency.
+*Prognosis is mainly affected by  the degree of deficiency  as well as the age of the patient. Evidence suggests that the majority of children younger than eight years of age with IgG subclass deficiency will normalize  IgG subclass level.<ref name="WolpertKnutsen1998">{{cite journal|last1=Wolpert|first1=Joshua|last2=Knutsen|first2=Alan P.|title=Natural History of Selective Antibody Deficiency to Bacterial Polysaccharide Antigens in Children|journal=Pediatric Asthma, Allergy & Immunology|volume=12|issue=3|year=1998|pages=183–191|issn=0883-1874|doi=10.1089/pai.1998.12.183}}</ref>
-*Evidence suggests that the majority of children younger than six to eight years of age with clinically significant IgG subclass deficiency and diminished specific antibody responses will normalize both antibody responsiveness and IgG subclass level(s) [10,41]. This appears to be particularly true for young children with IgG2 and IgA deficiency and impaired responses to polysaccharide antigens. In contrast, if the condition persists beyond the age of six years, it is likely to be permanent.
-*Adults with clinically significant IgG subclass deficiency and diminished specific antibody responses will rarely achieve normalization of a deficient IgG subclass level
+*Adults with clinically notable IgG subclass deficiency and diminished particular antibody responses will scarcely reach previous normal level of a deficient IgG subclass.
 *
 == Diagnosis ==
 ===Diagnostic Criteria===
-IgG subclass deficiency is a laboratory finding that does not necessarily equate to a clinical disorder. The diagnosis of a '''clinically significant''' IgG subclass deficiency requires evidence of antibody dysfunction in the form of recurrent infections and an inadequate response to vaccine challenge.
+IgG deficiency is a laboratory finding that may be not associated with significant clinical presentations. The diagnosis of a clinically significant IgG deficiency needs evidence of antibody dysfunction in the form of recurrent infections and an inadequate response to vaccine challenge.
-*The diagnosis of IgG deficiency is made when at least one of  the following two diagnostic criteria are met:
-:*low IgG subclass levels
+The diagnosis of IgG deficiency required the following two diagnostic criteria to meet in the clinical history of recurrent sinopulmonary infections''':'''<ref>{{Cite journal
-:*poor antibody response to vaccine challenge
+ | author = [[Francisco A. Bonilla]], [[David A. Khan]], [[Zuhair K. Ballas]], [[Javier Chinen]], [[Michael M. Frank]], [[Joyce T. Hsu]], [[Michael Keller]], [[Lisa J. Kobrynski]], [[Hirsh D. Komarow]], [[Bruce Mazer]], [[Robert P. Jr Nelson]], [[Jordan S. Orange]], [[John M. Routes]], [[William T. Shearer]], [[Ricardo U. Sorensen]], [[James W. Verbsky]], [[David I. Bernstein]], [[Joann Blessing-Moore]], [[David Lang]], [[Richard A. Nicklas]], [[John Oppenheimer]], [[Jay M. Portnoy]], [[Christopher R. Randolph]], [[Diane Schuller]], [[Sheldon L. Spector]], [[Stephen Tilles]] & [[Dana Wallace]]
+ | title = Practice parameter for the diagnosis and management of primary immunodeficiency
+ | journal = [[The Journal of allergy and clinical immunology]]
+ | volume = 136
+ | issue = 5
+ | pages = 1186–1205
+ | year = 2015
+ | month = November
+ | doi = 10.1016/j.jaci.2015.04.049
+ | pmid = 26371839
+}}</ref>
+#low IgG subclass levels
+#poor antibody response to the vaccine challenge
 === Symptoms ===
 *IgG deficiency is usually asymptomatic.
-*Symptoms of  IgG deficiency may include the symptoms of  recurrent sinopulmonary infections include otitis media, rhinosinusitis, and pneumonia and More serious infections that can occur include osteomyelitis, meningitis, septicemia, diarrhea, and various skin infections:
+*Symptoms of  IgG deficiency may include the symptoms of recurrent sinopulmonary infections include otitis media, rhinosinusitis, and pneumonia or even more serious infections that can occur such as osteomyelitis, meningitis, septicemia, diarrhea, and various skin infections.<ref name=":0">{{Cite journal
+ | author = [[H. G. Herrod]]
+ | title = Clinical significance of IgG subclasses
+ | journal = [[Current opinion in pediatrics]]
+ | volume = 5
+ | issue = 6
+ | pages = 696–699
+ | year = 1993
+ | month = December
+ | pmid = 8124421
+}}</ref>
 === Physical Examination ===
-*Physical examination of patients with longstanding immune defectsmay may be remarkable for:
+*Physical examination of patients with longstanding immune defects may be remarkable for''':'''<ref>{{Cite journal
-:*low body mass index (BMI)
+ | author = [[F. S. Rosen]], [[M. D. Cooper]] & [[R. J. Wedgwood]]
-:*scarring (of tympanic membranes or skin)
+ | title = The primary immunodeficiencies
-:*signs of chronic lung disease (chronic cough, absent gag reflex, clubbing, crackles, or wheezing to suggest bronchiectasis)
+ | journal = [[The New England journal of medicine]]
-:*ongoing infection (signs of chronic sinusitis, oral thrush, warts, or dermatophyte infections)
+ | volume = 333
+ | issue = 7
+ | pages = 431–440
+ | year = 1995
+ | month = August
+ | doi = 10.1056/NEJM199508173330707
+ | pmid = 7616993
+}}</ref>
+:*Low body mass index
+:*Scarring of tympanic membranes or skin
+:*Signs of chronic lung disease such as chronic cough, absent gag reflex, clubbing, crackles, or wheezing to suggest bronchiectasis
+:*Ongoing infection signs of chronic sinusitis, oral thrush, warts, or dermatophyte infections
 === Laboratory Findings ===
-*IgG subclass deficiency is a laboratory finding that does not necessarily equate to a clinical disorder.
+*IgG deficiency is a laboratory finding that may be not associated with significant clinical presentations. The normal amounts for IgG subclasses are wide and differ with the age of the patients.
-The normal ranges for IgG subclasses are broad and vary with the age of the population studied, presence or absence of disease, and the method of analysis (table 1) [2-9].
+For children 4 to 10 years of age, levels below the following are considered abnormal''':'''<ref>{{Cite journal
+ | author = [[L. A. Hanson]], [[R. Soderstrom]], [[A. Avanzini]], [[U. Bengtsson]], [[J. Bjorkander]] & [[T. Soderstrom]]
+ | title = Immunoglobulin subclass deficiency
+ | journal = [[The Pediatric infectious disease journal]]
+ | volume = 7
+ | issue = 5 Suppl
+ | pages = S17–S21
+ | year = 1988
+ | month = May
+ | pmid = 3041356
+}}</ref>
+* IgG1 level <250 mg/dL
+* IgG2 level <50 mg/dL
+* IgG3 level <15 mg/dL
+* IgG4 level <1 mg/dL
+For individuals older than 10 years of age, levels below the following are considered abnormal''':'''
+* IgG1 level <300 mg/dL
+* IgG2 level <50 mg/dL
+* IgG3 level <25 mg/dL
+* IgG4 level <1 mg/dL
-For children 4 to 10 years of age, levels below the following are considered abnormal:
+=== '''Vaccine Challenge Response''' ===
+IgG subclass deficiency is a laboratory finding which does not necessarily cause clinical presentations. For final diagnosis of IgG subclass deficiency, patients must be evaluated for antibody dysfunction in both polysaccharides and proteins antigens. The function can be assessed by measuring antibody titers to previously administered vaccines or natural infections. If titers are not in the protective range, a vaccine challenge should be performed  with the administration of vaccines with measurement of pre- and postimmunization titers
-●IgG1 level <250 mg/dL
+Titers of IgG antibodies to tetanus and diphtheria in vaccinated children and adults are used to evaluate immune responsiveness to protein antigens. Results are reported as IgG in general, although the antibody responses generated by these vaccines are largely (but not exclusively) composed of IgG1 and IgG3 antibodies, which is sometimes important in the evaluation of IgG subclass deficiency.<ref>{{Cite journal
+ | author = [[Jordan S. Orange]], [[Mark Ballow]], [[E. Richard Stiehm]], [[Zuhair K. Ballas]], [[Javier Chinen]], [[Maite De La Morena]], [[Dinakantha Kumararatne]], [[Terry O. Harville]], [[Paul Hesterberg]], [[Majed Koleilat]], [[Sean McGhee]], [[Elena E. Perez]], [[Jason Raasch]], [[Rebecca Scherzer]], [[Harry Schroeder]], [[Christine Seroogy]], [[Aarnoud Huissoon]], [[Ricardo U. Sorensen]] & [[Rohit Katial]]
+ | title = Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology
+ | journal = [[The Journal of allergy and clinical immunology]]
+ | volume = 130
+ | issue = 3 Suppl
+ | pages = S1–24
+ | year = 2012
+ | month = September
+ | doi = 10.1016/j.jaci.2012.07.002
+ | pmid = 22935624
+}}</ref>
-●IgG2 level <50 mg/dL
+'''Interpretation of Hib titers''' — The capsular polysaccharide polyribosylribitol phosphate (PRP) is an important antigen in immunity to ''Haemophilus influenzae'' type B (Hib). Anti-PRP IgG titers ≥1 mcg/mL are considered protective [28]. Although the polysaccharide PRP is the primary antigen, the conjugate vaccines employ either diphtheria toxoid or the outer membrane protein complex of meningococcus as the immunogenic protein. Therefore, antibodies to the Hib capsular polysaccharide in patients who received the conjugated Hib vaccine reflect a protein response, and protective antibodies against the PRP polysaccharide do not exclude unresponsiveness to the pure pneumococcal polysaccharides. Children in the United States have been receiving conjugated vaccines for prophylaxis against Hib since the early 1990s.
-●IgG3 level <15 mg/dL
+== Treatment ==
+=== Medical Therapy ===
+The mainstay of therapy for IgG deficiency includes the following ''':'''
+*Immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines<ref>{{Cite journal
+ | author = [[R. U. Sorensen]], [[L. E. Leiva]], [[P. A. Giangrosso]], [[B. Butler]], [[F. C. 3rd Javier]], [[D. M. Sacerdote]], [[N. Bradford]] & [[C. Moore]]
+ | title = Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine
+ | journal = [[The Pediatric infectious disease journal]]
+ | volume = 17
+ | issue = 8
+ | pages = 685–691
+ | year = 1998
+ | month = August
+ | pmid = 9726341
+}}</ref>
-●IgG4 level <1 mg/dL
+*
+*Aggressive management of asthma, allergic rhinitis predisposing to recurrent sinopulmonary infections
-For individuals older than 10 years of age, levels below the following are considered abnormal:
+*Recognition and treatment of sinopulmonary bacterial infections since infections are less likely to clear spontaneously in patients with antibody defects.
+*
+*Prophylactic antibiotics for patients with recurrent sinopulmonary infections. Evidence in support of this approach is largely derived from benefits observed in retrospective studies of children with this and similar antibody deficiencies.<ref name="WolpertKnutsen1998">{{cite journal|last1=Wolpert|first1=Joshua|last2=Knutsen|first2=Alan P.|title=Natural History of Selective Antibody Deficiency to Bacterial Polysaccharide Antigens in Children|journal=Pediatric Asthma, Allergy & Immunology|volume=12|issue=3|year=1998|pages=183–191|issn=0883-1874|doi=10.1089/pai.1998.12.183}}</ref>
-●IgG1 level <300 mg/dL
+*Intravenous or subcutaneous immune globulin replacement is indicated if the use of prophylactic antibiotics does not cause fewer infections or in patients with persistent and symptomatic chronic rhinosinusitis. This therapy should be reserved for patients with clearly impaired responses to protein and/or polysaccharide antigens.
+*Intravenous immune globulin therapy, at a standard dose range of 400 to 600 mg/kg, can be infused every three to four weeks.<ref name=":1">{{Cite journal
+ | author = [[Nabih I. Abdou]], [[Cindy A. Greenwell]], [[Reena Mehta]], [[Madhu Narra]], [[Jeffery D. Hester]] & [[John F. Halsey]]
+ | title = Efficacy of intravenous gammaglobulin for immunoglobulin G subclass and/or antibody deficiency in adults
+ | journal = [[International archives of allergy and immunology]]
+ | volume = 149
+ | issue = 3
+ | pages = 267–274
+ | year = 2009
+ | month =
+ | doi = 10.1159/000199723
+ | pmid = 19218820
+}}</ref> Immune globulin can also be replaced subcutaneously at weekly intervals.
+*Immune globulin therapy should be administered for one to two years initially, at which point the patient's status should be re-evaluated to determine if the number and/or severity of infections have been reduced. Not all patients with IgG subclass deficiencies benefit from immune globulin replacement, and the therapy should be discontinued if not effective in that individual.<ref>{{Cite journal
+ | author = [[Ann-Margreth Olinder-Nielsen]], [[Carl Granert]], [[Pia Forsberg]], [[Vanda Friman]], [[Auli Vietorisz]] & [[Janne Bjorkander]]
+ | title = Immunoglobulin prophylaxis in 350 adults with IgG subclass deficiency and recurrent respiratory tract infections: a long-term follow-up
+ | journal = [[Scandinavian journal of infectious diseases]]
+ | volume = 39
+ | issue = 1
+ | pages = 44–50
+ | year = 2007
+ | month =
+ | doi = 10.1080/00365540600951192
+ | pmid = 17366012
+}}</ref>
-●IgG2 level <50 mg/dL
+*
-●IgG3 level <25 mg/dL
-●IgG4 level <1 mg/dL
-=== '''Vaccine Challange Response''' ===
-IgG subclass deficiency is a laboratory finding that does not necessarily equate to a clinical disorder. The diagnosis of a '''clinically significant''' IgG subclass deficiency requires evidence of antibody dysfunction in the form of recurrent infections and an inadequate response to vaccine challenge.
-Vaccine response is part of the evaluation of possible immunodeficiency. The clinical indications for assessing vaccine responsiveness include frequent and recurrent sinopulmonary or ear infections, chronic gastrointestinal infections, any severe or unusual infections, and abnormal need for antibiotics (table 1). Most patients have already had serum levels of immunoglobulin (Ig)G, IgA, and IgM measured, but if not, these can be obtained at the same time that vaccine response is assessed. The different warning signs of immunodeficiency are reviewed in more detail elsewhere:
-Titers of IgG antibodies to tetanus and diphtheria in vaccinated children and adults are used to evaluate immune responsiveness to protein antigens. Results are reported as IgG in general, although the antibody responses generated by these vaccines are largely (but not exclusively) composed of IgG1 and IgG3 antibodies, which is sometimes important in evaluation of IgG subclass deficiency.
-'''Interpretation of Hib titers''' — The capsular polysaccharide polyribosylribitol phosphate (PRP) is an important antigen in immunity to ''Haemophilus influenzae'' type B (Hib). Anti-PRP IgG titers ≥1 mcg/mL are considered protective [28]. Although the polysaccharide PRP is the primary antigen, the conjugate vaccines employ either diphtheria toxoid or the outer membrane protein complex of meningococcus as the immunogenic protein. Therefore, antibodies to the Hib capsular polysaccharide in patients who received the conjugated Hib vaccine reflect a protein response, and protective antibodies against the PRP polysaccharide do not exclude unresponsiveness to the pure pneumococcal polysaccharides. Children in the United States have been receiving conjugated vaccines for prophylaxis against Hib since the early 1990s.
-== Treatment ==
-=== Medical Therapy ===
-*The mainstay of therapy for IgG deficiency includes the following:
-*●Immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines
-*All patients with IgG subclass deficiency and poor responses to polysaccharide vaccines should receive a conjugated pneumococcal vaccine in order to boost immunity to this common respiratory pathogen.  ●Aggressive management of other conditions predisposing to recurrent sinopulmonary infections (eg, asthma, allergic rhinitis)
-*Aggressive management of any conditions predisposing to recurrent sinopulmonary infections (especially allergic rhinitis and asthma) is critical to improving the clinical outcome of patients with IgG subclass deficiency. Atopic disorders occurred in 55 to 58 percent of the children with SAD with or without IgG2-IgA deficiency in one report   ●Increased vigilance and appropriate antibiotic therapy for infections
-*Prompt recognition and treatment of sinopulmonary bacterial infections is a significant component of management of these patients, since infections are less likely to clear spontaneously in patients with antibody defects.  ●Prophylactic antibiotics
-*Patients with recurrent sinopulmonary infections, despite the previously described measures, usually require prophylactic antibiotics. Evidence in support of this approach is largely derived from benefits observed in retrospective studies of children with this and similar antibody deficiencies.  ●Intravenous or subcutaneous immune globulin replacement
-*Judicious use of immune globulin therapy is appropriate if the use of prophylactic antibiotics does not result in fewer infections and/or in patients with persistent and symptomatic chronic rhinosinusitis. This therapy should be reserved for patients with clearly impaired responses to protein and/or polysaccharide antigens [93-95]. Most of the patients requiring this intervention have impaired antibody responses to bacterial polysaccharide antigens with IgG2 +/-IgG4 deficiency, although there are reported cases of benefit in IgG3 deficiency as well [71]. Intravenous immune globulin therapy, at a standard dose range of 400 to 600 mg/kg, can be infused every three to four weeks [96]. Immune globulin can also be replaced subcutaneously at weekly intervals. (See "Immune globulin therapy in primary immunodeficiency".)  Patients with selective IgG4 or IgG3 deficiency usually have normal antibody responses, although differing degrees of impaired specific antibody responses in patients with IgG3 deficiency have been noted [73,97,98]. The role of immune globulin in these patients is not as clear. However, several studies have reported clinical improvement in patients with IgG3 deficiency as a result of this intervention [73,97,99,100]. In the largest study, which included 33 patients with IgG3 deficiency, patients with more than four antibiotic-requiring RTIs per year were treated with immune globulin, and the number of infections before and during treatment was compared [100]. Reduction in the number of RTIs was seen in 29 of 33 patients with IgG3 deficiency: 23 experienced a ≥50 percent reduction, and 6 had a reduction of <50 percent.  Immune globulin therapy should be administered for one to two years initially, at which point the patient's status should be re-evaluated to determine if the number and/or severity of infections have been reduced. Not all patients with IgG subclass deficiencies benefit from immune globulin replacement, and the therapy should be discontinued if not effective in that individual [100].
-*
 === Prevention ===
 *There are no primary preventive measures available for IgG deficiency.
-*Secondary prevention strategies following IgG deficiency include avoidance measures, vaccination, prophylactic antibiotics, immune globulin therapy,and when infections do occur, broader spectrum and more prolonged antibiotics are often required.
+*Secondary and tertiary prevention strategies following IgG deficiency include avoidance measures, vaccination, prophylactic antibiotics, immune globulin therapy,and when infections do occur, broader spectrum and more prolonged antibiotics are often recommended.
-*Avoidance: to reduce exposure to others with potentially contagious illnesses: proper handwashing and use of alcohol-based disinfectants should be provided to patients and their families Co-sleeping among family members should be minimized, and immunization of family members and close contacts
+*Avoidance: to reduce exposure to others with potentially contagious illnesses: proper handwashing and use of alcohol-based disinfectants should be provided to patients and their families; Co-sleeping among family members should be minimized, and immunization of family members and close contacts
 *Careful attention should be paid to patient's oral hygiene and dental health.
-*'''Vaccination Immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines Advisory Committee on Immunization Practices (ACIP)<ref>{{Cite journal
+*Vaccination Immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines Advisory Committee on Immunization Practices (ACIP)'''<ref>{{Cite journal
   | author = [[R. U. Sorensen]], [[L. E. Leiva]], [[P. A. Giangrosso]], [[B. Butler]], [[F. C. 3rd Javier]], [[D. M. Sacerdote]], [[N. Bradford]] & [[C. Moore]]
   | title = Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine
@@ Line 341: / Line 574: @@
   | pmid = 9726341
 }}</ref>'''
-*recommended that conjugated Hib vaccine be administered in patients with IgG2 subclass deficiency and those with specific antibody deficiency (SAD)  <ref>{{Cite journal
+*Recommended that conjugated Hib vaccine be administered in patients with IgG2 subclass deficiency and those with specific antibody deficiency (SAD)  <ref>{{Cite journal
   | author = [[R. U. Sorensen]], [[L. E. Leiva]], [[P. A. Giangrosso]], [[B. Butler]], [[F. C. 3rd Javier]], [[D. M. Sacerdote]], [[N. Bradford]] & [[C. Moore]]
   | title = Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine
@@ Line 363: / Line 596: @@
   | pmid = 24311479
 }}</ref>
-*'''ANTIMICROBIAL THERAPY''' Treating acute infections  Prophylactic antimicrobial therapy Patients with recurrent sinopulmonary infections, despite the previously described measures, usually require prophylactic antibiotics
+*Antimicrobial therapy: Treating acute infections  and prophylactic antimicrobial therapy among patients with recurrent sinopulmonary infections or ongoing lung disease  is helpful. Thus, immediate recognition and treatment with antibiotics can help prevent chronic infections and infectious complications. It is important to ensure that the infection has treated completely at the end of a course of antibiotics, as patients with immunodeficiency sometimes necessitate longer durations of therapy. Antibiotic resistance does not seem to be a serious problem in patients with primary immunodeficiency, for causes which are not clearly understood, then the same antibiotics continue to be useful, regardless of prolonged or frequent exposure.<ref>{{Cite journal
+ | author = [[A. Samuelson]], [[S. Borrelli]], [[R. Gustafson]], [[L. Hammarstrom]], [[C. I. Smith]], [[J. Jonasson]] & [[A. A. Lindberg]]
+ | title = Characterization of Haemophilus influenzae isolates from the respiratory tract of patients with primary antibody deficiencies: evidence for persistent colonizations
+ | journal = [[Scandinavian journal of infectious diseases]]
+ | volume = 27
+ | issue = 4
+ | pages = 303–313
+ | year = 1995
+ | month =
+ | pmid = 8658061
+}}</ref>
 ==References==