Predominantly antibody deficiency: Difference between revisions
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*It is caused by mutation of µ heavy chain(IGHM) on [[chromosome]] 14. <ref name="pmid8890099">{{cite journal |vauthors=Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trübel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME |title=Mutations in the mu heavy-chain gene in patients with agammaglobulinemia |journal=N. Engl. J. Med. |volume=335 |issue=20 |pages=1486–93 |date=November 1996 |pmid=8890099 |doi=10.1056/NEJM199611143352003 |url=}}</ref> | *It is caused by mutation of µ heavy chain(IGHM) on [[chromosome]] 14. <ref name="pmid8890099">{{cite journal |vauthors=Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trübel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME |title=Mutations in the mu heavy-chain gene in patients with agammaglobulinemia |journal=N. Engl. J. Med. |volume=335 |issue=20 |pages=1486–93 |date=November 1996 |pmid=8890099 |doi=10.1056/NEJM199611143352003 |url=}}</ref> | ||
*This mutation is phenotypically similar to [[X-linked agammaglobulinemia]], but unlike [[X-linked agammaglobulinemia]] can also be seen in females, yet there has been a study that provides data showing clinically significant difference between the two.<ref name="pmid26910880">{{cite journal |vauthors=Abolhassani H, Vitali M, Lougaris V, Giliani S, Parvaneh N, Parvaneh L, Mirminachi B, Cheraghi T, Khazaei H, Mahdaviani SA, Kiaei F, Tavakolinia N, Mohammadi J, Negahdari B, Rezaei N, Hammarstrom L, Plebani A, Aghamohammadi A |title=Cohort of Iranian Patients with Congenital Agammaglobulinemia: Mutation Analysis and Novel Gene Defects |journal=Expert Rev Clin Immunol |volume=12 |issue=4 |pages=479–86 |date=2016 |pmid=26910880 |doi=10.1586/1744666X.2016.1139451 |url=}}</ref> | *This mutation is phenotypically similar to [[X-linked agammaglobulinemia]], but unlike [[X-linked agammaglobulinemia]] can also be seen in females, yet there has been a study that provides data showing clinically significant difference between the two.<ref name="pmid26910880">{{cite journal |vauthors=Abolhassani H, Vitali M, Lougaris V, Giliani S, Parvaneh N, Parvaneh L, Mirminachi B, Cheraghi T, Khazaei H, Mahdaviani SA, Kiaei F, Tavakolinia N, Mohammadi J, Negahdari B, Rezaei N, Hammarstrom L, Plebani A, Aghamohammadi A |title=Cohort of Iranian Patients with Congenital Agammaglobulinemia: Mutation Analysis and Novel Gene Defects |journal=Expert Rev Clin Immunol |volume=12 |issue=4 |pages=479–86 |date=2016 |pmid=26910880 |doi=10.1586/1744666X.2016.1139451 |url=}}</ref> | ||
*Treatment is mainly via replacement of immunoglobulins by intravenous or subcutaneous routes, haematopoietic stem cell therapy and use of prophylactic and curative [[antibiotics]].<ref name=" | *Treatment is mainly via replacement of immunoglobulins by intravenous or subcutaneous routes, haematopoietic stem cell therapy and use of prophylactic and curative [[antibiotics]].<ref name="pmid21466548">{{cite journal |vauthors=Cunningham-Rundles C |title=Key aspects for successful immunoglobulin therapy of primary immunodeficiencies |journal=Clin. Exp. Immunol. |volume=164 Suppl 2 |issue= |pages=16–9 |date=June 2011 |pmid=21466548 |pmc=3087906 |doi=10.1111/j.1365-2249.2011.04390.x |url=}}</ref> | ||
==Igα Deficiency== | ==Igα Deficiency== | ||
Revision as of 16:20, 29 November 2018
|
Immunodeficiency Main Page |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.[2], Anmol Pitliya, M.B.B.S. M.D.[3]
Overview
Classification
| Predominantly antibody deficiencies | |||||||||||||||
| Hypogammaglobulinemia | Other antibody deficiencies | ||||||||||||||
Hypogammaglobulinemia
| Predominantly antibody deficiencies (A): Hypogammaglobulinemia | |||||||||||||||||||||||||||||||
| Serum immunoglobulin assays : IgG, IgA, IgM, IgE | |||||||||||||||||||||||||||||||
| IgG, IgA, and/or IgM ↓↓ → B Lymphocyte (CD19+) enumeration (CMF) | |||||||||||||||||||||||||||||||
| B absent | B >1% | ||||||||||||||||||||||||||||||
| X-Linked Agammaglobulinemia | Common Variable Immunodeficiency Phenotype | CD19 deficiency | |||||||||||||||||||||||||||||
| µ heavy chain Def | CVID with no gene defect specified | CD20 deficiency | |||||||||||||||||||||||||||||
| Igα def | PIK3CD mutation(GOF),PIK3R1 deficiency(LOF) | CD21 deficiency | |||||||||||||||||||||||||||||
| Igβ def | PTEN deficiency(LOF) | TRNT1 deficiency | |||||||||||||||||||||||||||||
| BLNK def | CD81 deficiency | NFKB1 deficiency | |||||||||||||||||||||||||||||
| λ5 def | TACI deficiency | NFKB2 deficiency | |||||||||||||||||||||||||||||
| PI3KR1 def | BAFF receptor deficiency | IKAROS deficiency | |||||||||||||||||||||||||||||
| E47 transcription factor def | TWEAK deficiency | ATP6AP1 deficiency | |||||||||||||||||||||||||||||
| Mannosyl-oligosaccharide glucosidase deficiency (MOGS) | |||||||||||||||||||||||||||||||
| TTC37 deficiency | |||||||||||||||||||||||||||||||
| IRF2BP2 deficiency | |||||||||||||||||||||||||||||||
Other Antibody deficiencies
| Predominantly antibody deficiencies (B): Other antibody deficiencies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Serum Immunolobulin Assays: IgG, IgA, IgM, IgE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe Reduction in Serum IgG and IgA with NI/elevated IgM and Normal Numbers of B cells: Hyper IgM Syndromes | Isotype, Light Chain, or Functional Deficiencies with Generally NI Numbers of B cells | High B cell numbers due to constitutive NF-kB activation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| AID deficiency | Selective IgA deficiency | CARD11 Gain of Function | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UNG deficiency | Transient hypogammaglobuliemia of infancy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| INO80 | IgG subclass deficiency with IgA deficiency | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MSH6 | Isolated IgG subclass deficiency | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Specific antibody deficiency with normal Ig levels and normal B cells | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ig heavy chain muations and deletions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kappa chain deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Selective IgM deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
X-linked Agammaglobulinemia
It is an X linked disease first described by Bruton in 1952.It is caused by the mutation of BTK gene (present on the long arm of X chromosome) which encodes for the protein Bruton tyrosine kinase,[1]which is mainly associated with the maturation and differentiation of the pre B cell. The disruption of this protein can therefore lead to significant decrease in all antibody isotypes, due to failure of Ig heavy chain rearrangement. [2]
- Affected individuals generally present between 3 months to 3 years of age, with almost 90% becoming symptomatic by 5 years of age.[3]
- Presence of maternal immunoglobulins provide transient protection, concealing symptoms of the disease and preventing early detection.
- Physical examination typically shows absence of lymph nodes.
- Patients are susceptible to recurrent infections with encapsulated organisms and enteroviruses, primarily effecting respiratory and gastrointestinal tracts.
- Laboratory findings show defect in humoral immunity with absence or negligible amount of IgM, IgG, and IgA, as well as <2% of B cells lymphocytes. Neutropenia can also be seen.[4] [1][5]
- Treatment is mainly via haematopoietic stem cell therapy and through replacement of immunoglobulins either by intravenous or subcutaneous routes. Recurrent infections are prevented and treated by antibiotics.[6]
For more information on X-linked agammaglobulinemia, click here.
µ Heavy Chain Deficiency
- Autosomal recessive (AR) transmission.
- It is caused by mutation of µ heavy chain(IGHM) on chromosome 14. [7]
- This mutation is phenotypically similar to X-linked agammaglobulinemia, but unlike X-linked agammaglobulinemia can also be seen in females, yet there has been a study that provides data showing clinically significant difference between the two.[8]
- Treatment is mainly via replacement of immunoglobulins by intravenous or subcutaneous routes, haematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[6]
Igα Deficiency
- Autosomal recessive (AR) transmission.
- Mutation of Igα(CD79α) a component of B cell receptor(BCR). Mutations in Pre-BCR complex many times lead to truncation of B cell development.
- It causes a B cell defect which leads to a clinical picture similar to X-linked agammaglobulinemia.
- Patients have increased susceptibility to bacterial infections and otitis media.
- Diagnosis is mainly by polymerase chain reaction (PCR) or single starnd conformational polymosrphism analysis(SSCA).[9]
- Treatment is mainly through replacement of immunoglobulins by intravenous or subcutaneous routes, haematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[10]
Igβ Deficiency
- Autosomal recessive (AR) transmission.
- Caused by mutation in the CD79B gene on chromosome 17.
- Ig is a signal transducton molecule like Ig and is essential for B cell receptor(BCR) expression.
- Patients generally present with reduced immunoglobulins which leads to frequent bacterial infections of upper and lower respiratory tract similar to other agammaglobulinemia like X-linked agammaglobulinemia.[11][12]
- Treatment is mainly via replacement of immunoglobulins by intravenous or subcutaneous routes, haematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[12]
BLNK Deficiency
- Autosomal recessive (AR) transmission.
- BLNK gene on chromosome 10 encodes for a scaffold molecule B cell linker protein (BLNK, SLC-65) and is crucial for the development of pre B cell.
- Patients generally present with recurrent bacterial infections, otitis media and upper and lower respiratory tract infections simillar to X-linked agammaglobulinemia.[13]
- Treatment is mainly via replacement of immunoglobulins by intravenous or subcutaneous routes, haematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[10]
λ5 Deficiency
- Autosomal recessive (AR) transmission.
- It is caused by mutation of λ5(IGLL1), component of B cell receptor, on chromosome 22.
- Leads to clinical features similar to X-linked agammaglobulinemia.[14]
- Treatment is mainly through replacement of immunoglobulins by intravenous or subcutaneous routes, haematopoietic stem cell therapy and use of prophylactic and curative antibiotics
PI3KR1 Deficiency
E47 transcription factor Deficiency
- Mutation of E47 transcription factor.
- This mutation leads to improper differnetiation of B cell from lymphoid precursors.[15]
- Patients present with few B cells characterized increased expression of CD19, but without B cell receptor (BCR).[16]
- Treatment
References
- ↑ 1.0 1.1 Hernandez-Trujillo VP, Scalchunes C, Cunningham-Rundles C, Ochs HD, Bonilla FA, Paris K, Yel L, Sullivan KE (August 2014). "Autoimmunity and inflammation in X-linked agammaglobulinemia". J. Clin. Immunol. 34 (6): 627–32. doi:10.1007/s10875-014-0056-x. PMC 4157090. PMID 24909997.
- ↑ Rawlings DJ, Witte ON (April 1994). "Bruton's tyrosine kinase is a key regulator in B-cell development". Immunol. Rev. 138: 105–19. PMID 8070812.
- ↑ Winkelstein JA, Marino MC, Lederman HM, Jones SM, Sullivan K, Burks AW, Conley ME, Cunningham-Rundles C, Ochs HD (July 2006). "X-linked agammaglobulinemia: report on a United States registry of 201 patients". Medicine (Baltimore). 85 (4): 193–202. doi:10.1097/01.md.0000229482.27398.ad. PMID 16862044.
- ↑ Fried AJ, Bonilla FA (July 2009). "Pathogenesis, diagnosis, and management of primary antibody deficiencies and infections". Clin. Microbiol. Rev. 22 (3): 396–414. doi:10.1128/CMR.00001-09. PMC 2708392. PMID 19597006.
- ↑ Berglöf A, Turunen JJ, Gissberg O, Bestas B, Blomberg KE, Smith CI (December 2013). "Agammaglobulinemia: causative mutations and their implications for novel therapies". Expert Rev Clin Immunol. 9 (12): 1205–21. doi:10.1586/1744666X.2013.850030. PMID 24215410.
- ↑ 6.0 6.1 Cunningham-Rundles C (June 2011). "Key aspects for successful immunoglobulin therapy of primary immunodeficiencies". Clin. Exp. Immunol. 164 Suppl 2: 16–9. doi:10.1111/j.1365-2249.2011.04390.x. PMC 3087906. PMID 21466548.
- ↑ Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trübel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME (November 1996). "Mutations in the mu heavy-chain gene in patients with agammaglobulinemia". N. Engl. J. Med. 335 (20): 1486–93. doi:10.1056/NEJM199611143352003. PMID 8890099.
- ↑ Abolhassani H, Vitali M, Lougaris V, Giliani S, Parvaneh N, Parvaneh L, Mirminachi B, Cheraghi T, Khazaei H, Mahdaviani SA, Kiaei F, Tavakolinia N, Mohammadi J, Negahdari B, Rezaei N, Hammarstrom L, Plebani A, Aghamohammadi A (2016). "Cohort of Iranian Patients with Congenital Agammaglobulinemia: Mutation Analysis and Novel Gene Defects". Expert Rev Clin Immunol. 12 (4): 479–86. doi:10.1586/1744666X.2016.1139451. PMID 26910880.
- ↑ Wang Y, Kanegane H, Sanal O, Tezcan I, Ersoy F, Futatani T, Miyawaki T (April 2002). "Novel Igalpha (CD79a) gene mutation in a Turkish patient with B cell-deficient agammaglobulinemia". Am. J. Med. Genet. 108 (4): 333–6. PMID 11920841.
- ↑ 10.0 10.1 Bardakhch'ian EA, Makliakov I, Karkishchenko NN, Kharlanova NG (1992). "[Benzodiazepine receptors of the neurons and astrocytes]". Eksp Klin Farmakol (in Russian). 55 (2): 6–9. PMID 1330145. Vancouver style error: initials (help)
- ↑ Ferrari S, Lougaris V, Caraffi S, Zuntini R, Yang J, Soresina A, Meini A, Cazzola G, Rossi C, Reth M, Plebani A (September 2007). "Mutations of the Igbeta gene cause agammaglobulinemia in man". J. Exp. Med. 204 (9): 2047–51. doi:10.1084/jem.20070264. PMC 2118692. PMID 17709424.
- ↑ 12.0 12.1 Dobbs AK, Yang T, Farmer D, Kager L, Parolini O, Conley ME (August 2007). "Cutting edge: a hypomorphic mutation in Igbeta (CD79b) in a patient with immunodeficiency and a leaky defect in B cell development". J. Immunol. 179 (4): 2055–9. PMID 17675462.
- ↑ Minegishi Y, Rohrer J, Coustan-Smith E, Lederman HM, Pappu R, Campana D, Chan AC, Conley ME (December 1999). "An essential role for BLNK in human B cell development". Science. 286 (5446): 1954–7. PMID 10583958.
- ↑ Minegishi Y, Coustan-Smith E, Wang YH, Cooper MD, Campana D, Conley ME (January 1998). "Mutations in the human lambda5/14.1 gene result in B cell deficiency and agammaglobulinemia". J. Exp. Med. 187 (1): 71–7. PMC 2199185. PMID 9419212.
- ↑ Boisson B, Wang YD, Bosompem A, Ma CS, Lim A, Kochetkov T, Tangye SG, Casanova JL, Conley ME (November 2013). "A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells". J. Clin. Invest. 123 (11): 4781–5. doi:10.1172/JCI71927. PMC 3809807. PMID 24216514.
- ↑ Dobbs AK, Bosompem A, Coustan-Smith E, Tyerman G, Saulsbury FT, Conley ME (August 2011). "Agammaglobulinemia associated with BCR⁻ B cells and enhanced expression of CD19". Blood. 118 (7): 1828–37. doi:10.1182/blood-2011-01-330472. PMC 3158715. PMID 21693761.