Phenocopies of primary immunodeficiency: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
 
(30 intermediate revisions by 2 users not shown)
Line 2: Line 2:
{{ID}}
{{ID}}


{{CMG}}; {{AE}} {{Akram}}, {{Anmol}}
{{CMG}}; {{AE}} {{Sab}}, {{Akram}}, {{Anmol}}


==Overview==
==Overview==
These disorders behave and present like primary PIDs, but they are acquired secondary to the occurrence of autoantibodies or somatic mutations.<ref name="pmid26454309">{{cite journal| author=Raje N, Dinakar C| title=Overview of Immunodeficiency Disorders. | journal=Immunol Allergy Clin North Am | year= 2015 | volume= 35 | issue= 4 | pages= 599-623 | pmid=26454309 | doi=10.1016/j.iac.2015.07.001 | pmc=4600970 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26454309  }} </ref>These conditions are not caused by inherited genetic mutations, but instead are acquired during life.


==Classification==
==Classification==
Line 11: Line 12:
{{Family tree | | | | | A01 | | | | |A01=Phenocopies of PID}}
{{Family tree | | | | | A01 | | | | |A01=Phenocopies of PID}}
{{Family tree | | |,|-|-|^|-|-|.| | |}}
{{Family tree | | |,|-|-|^|-|-|.| | |}}
{{Family tree | | B01 | | | | | B02 | | |B01=Associated with Somatic Mutations|B02=Associated with Auto-Antibodies}}
{{Family tree | | B01 | | | | B02 | | |B01=Associated with somatic mutations|B02=Associated with auto-antibodies}}
{{Family tree | |!| | | | | | |!| | | | |}}
{{Family tree | |!| | | | | |!| | | | |}}
{{Family tree | |)| C01 | | | |)| D01 | |C01=ALPS-SFAS|D01=Chronic mucocutaneous candidiasis}}
{{Family tree | |)| C01 | | |)| D01 | |C01=ALPS-SFAS|D01=Chronic mucocutaneous candidiasis}}
{{Family tree | |!| | | | | | |!| | | | |}}
{{Family tree | |!| | | | | |!| | | | |}}
{{Family tree | |)| C02 | | | |)| D02 | |C02=RALD(RAS-associated autoimmune leukoproliferative disease)|D02=Adult-onset immunodeficiency with susceptibility to mycobacteria}}
{{Family tree | |)| C02 | | |)| D02 | |C02=RALD (RAS-associated autoimmune leukoproliferative disease)|D02=Adult-onset immunodeficiency with susceptibility to mycobacteria}}
{{Family tree | |!| | | | | | |!| | | | |}}
{{Family tree | |!| | | | | |!| | | | |}}
{{Family tree | |)| C03 | | | |)| D03 | |C03=Cryopyrinopathy(Muckle-Wells Syndrome)|D03=Recurrentt skin infections}}
{{Family tree | |)| C03 | | |)| D03 | |C03=Cryopyrinopathy (Muckle-Wells Syndrome)|D03=Recurrent skin infections}}
{{Family tree | |!| | | | | | |!| | | | | |}}
{{Family tree | |!| | | | | |!| | | | | |}}
{{Family tree | |`| C04 | | | |)| D04 | | |C04=Hypereosinophilic syndrome due to somatic mutations in STAT5b|D04=Pulmonary alveolar proteinosis}}
{{Family tree | |`| C04 | | |)| D04 | | |C04=[[Hypereosinophilic syndrome|Hypereosinophilic syndrome due to somatic mutations in STAT5b]]|D04=[[Pulmonary alveolar proteinosis]]}}
{{Family tree | | | | | | | | |!| | | | | |}}
{{Family tree | | | | | | | |!| | | | | |}}
{{Family tree | | | | | | | | |)| D05 | | |D05=Acquired angiooedema}}
{{Family tree | | | | | | | |)| D05 | | |D05=[[Angioedema|Acquired angioedema]]}}
{{Family tree | | | | | | | | |!| | | | | |}}
{{Family tree | | | | | | | |!| | | | | |}}
{{Family tree | | | | | | | | |)| D06 | | |D06=Atypical Hemolytic Uremic Syndrome}}
{{Family tree | | | | | | | |)| D06 | | |D06=[[Hemolytic uremic syndrome|Atypical hemolytic uremic syndrome]]}}
{{Family tree | | | | | | | | |!| | | | | |}}
{{Family tree | | | | | | | |!| | | | | |}}
{{Family tree | | | | | | | | |`| D07 | | |D07=Thymoma with hypogammaglobulinemia}}
{{Family tree | | | | | | | |`| D07 | | |D07=[[Thymoma|Thymoma with hypogammaglobulinemia]]}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree/end}}
{{Family tree/end}}


==ALPS-SFAS==
==Autoimmune Lymphoproliferative Syndrome due to Somatic FAS Mutations (ALPS-SFAS)==
*Heritable disorder of apoptosis, resulting in the accumulation of autoreactive lymphocytes.<ref name="pmid20360470">{{cite journal| author=Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB et al.| title=Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome. | journal=Blood | year= 2010 | volume= 115 | issue= 25 | pages= 5164-9 | pmid=20360470 | doi=10.1182/blood-2010-01-263145 | pmc=2892951 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20360470  }} </ref>
*ALPS-SFAS is a heritable disorder of [[apoptosis]], resulting in the accumulation of autoreactive [[lymphocytes]].<ref name="pmid20360470">{{cite journal| author=Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB et al.| title=Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome. | journal=Blood | year= 2010 | volume= 115 | issue= 25 | pages= 5164-9 | pmid=20360470 | doi=10.1182/blood-2010-01-263145 | pmc=2892951 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20360470  }} </ref>
*Manifests in early childhood as nonmalignant lymphadenopathy with hepatosplenomegaly and autoimmune cytopenias.<ref name="pmid20360470">{{cite journal| author=Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB et al.| title=Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome. | journal=Blood | year= 2010 | volume= 115 | issue= 25 | pages= 5164-9 | pmid=20360470 | doi=10.1182/blood-2010-01-263145 | pmc=2892951 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20360470  }} </ref>
*Manifests in early childhood as nonmalignant [[lymphadenopathy]] with [[hepatosplenomegaly]] and [[Autoimmunity|autoimmune]] [[Cytopenia|cytopenias]].
*Patients with mutations have developed B and T-cell lymphomas.<ref name="pmid11418480">{{cite journal| author=Straus SE, Jaffe ES, Puck JM, Dale JK, Elkon KB, Rösen-Wolff A et al.| title=The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis. | journal=Blood | year= 2001 | volume= 98 | issue= 1 | pages= 194-200 | pmid=11418480 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11418480  }} </ref>
*Patients with mutations have developed B and T-cell [[Lymphoma|lymphomas]].<ref name="pmid11418480">{{cite journal| author=Straus SE, Jaffe ES, Puck JM, Dale JK, Elkon KB, Rösen-Wolff A et al.| title=The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis. | journal=Blood | year= 2001 | volume= 98 | issue= 1 | pages= 194-200 | pmid=11418480 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11418480  }} </ref>
*Peripheral blood analysis in patients has demonstrated hypergammaglobulinemia along with increased numbers of B and T lymphocytes.<ref name="pmid1386609">{{cite journal| author=Sneller MC, Straus SE, Jaffe ES, Jaffe JS, Fleisher TA, Stetler-Stevenson M et al.| title=A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease. | journal=J Clin Invest | year= 1992 | volume= 90 | issue= 2 | pages= 334-41 | pmid=1386609 | doi=10.1172/JCI115867 | pmc=443107 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1386609  }} </ref>
*Peripheral blood analysis in patients has demonstrated [[hypergammaglobulinemia]] along with increased numbers of B and T lymphocytes.<ref name="pmid1386609">{{cite journal| author=Sneller MC, Straus SE, Jaffe ES, Jaffe JS, Fleisher TA, Stetler-Stevenson M et al.| title=A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease. | journal=J Clin Invest | year= 1992 | volume= 90 | issue= 2 | pages= 334-41 | pmid=1386609 | doi=10.1172/JCI115867 | pmc=443107 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1386609  }} </ref>
*Some studies have demonstrated that ALPS is compatible with long-term survival.<ref name="pmid8929361">{{cite journal| author=Drappa J, Vaishnaw AK, Sullivan KE, Chu JL, Elkon KB| title=Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. | journal=N Engl J Med | year= 1996 | volume= 335 | issue= 22 | pages= 1643-9 | pmid=8929361 | doi=10.1056/NEJM199611283352204 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8929361  }} </ref><ref name="pmid4165068">{{cite journal| author=Canale VC, Smith CH| title=Chronic lymphadenopathy simulating malignant lymphoma. | journal=J Pediatr | year= 1967 | volume= 70 | issue= 6 | pages= 891-9 | pmid=4165068 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4165068  }} </ref>
*Some studies have demonstrated that ALPS is compatible with long-term survival.<ref name="pmid8929361">{{cite journal| author=Drappa J, Vaishnaw AK, Sullivan KE, Chu JL, Elkon KB| title=Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. | journal=N Engl J Med | year= 1996 | volume= 335 | issue= 22 | pages= 1643-9 | pmid=8929361 | doi=10.1056/NEJM199611283352204 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8929361  }} </ref><ref name="pmid4165068">{{cite journal| author=Canale VC, Smith CH| title=Chronic lymphadenopathy simulating malignant lymphoma. | journal=J Pediatr | year= 1967 | volume= 70 | issue= 6 | pages= 891-9 | pmid=4165068 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4165068  }} </ref>


===Types of mutation===
==RAS-Associated Autoimmune Leukoproliferative Disease (RALD)==
*Type IA is caused by heterozygous mutation in the FAS gene (TNFRSF6, or CD95)
*RALD is a leukoproliferative disorder characterized by [[lymphadenopathy]], [[splenomegaly]], and variable [[autoimmune]] phenomena, including [[autoimmune hemolytic anemia]], [[idiopathic thrombocytopenic purpura]], and [[neutropenia]].<ref name="pmid24240292">{{cite journal| author=Oliveira JB| title=The expanding spectrum of the autoimmune lymphoproliferative syndromes. | journal=Curr Opin Pediatr | year= 2013 | volume= 25 | issue= 6 | pages= 722-9 | pmid=24240292 | doi=10.1097/MOP.0000000000000032 | pmc=4435794 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24240292  }} </ref><ref name="pmid21079152">{{cite journal| author=Niemela JE, Lu L, Fleisher TA, Davis J, Caminha I, Natter M et al.| title=Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. | journal=Blood | year= 2011 | volume= 117 | issue= 10 | pages= 2883-6 | pmid=21079152 | doi=10.1182/blood-2010-07-295501 | pmc=3062298 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21079152  }} </ref>
*Type Ib is caused by heterozygous mutation in the FAS ligand (FASL) gene (TNFSF6 or CD95L)
==RALD(RAS-associated autoimmune leukoproliferative disease)==
*Originally considered a subtype of RAS due to the significant overlap.<ref name="pmid24240292">{{cite journal| author=Oliveira JB| title=The expanding spectrum of the autoimmune lymphoproliferative syndromes. | journal=Curr Opin Pediatr | year= 2013 | volume= 25 | issue= 6 | pages= 722-9 | pmid=24240292 | doi=10.1097/MOP.0000000000000032 | pmc=4435794 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24240292  }} </ref><ref name="pmid21079152">{{cite journal| author=Niemela JE, Lu L, Fleisher TA, Davis J, Caminha I, Natter M et al.| title=Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. | journal=Blood | year= 2011 | volume= 117 | issue= 10 | pages= 2883-6 | pmid=21079152 | doi=10.1182/blood-2010-07-295501 | pmc=3062298 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21079152  }} </ref>
*A leukoproliferative disorder characterized by lymphadenopathy, splenomegaly, and variable autoimmune phenomena, including autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, and neutropenia.<ref name="pmid24240292">{{cite journal| author=Oliveira JB| title=The expanding spectrum of the autoimmune lymphoproliferative syndromes. | journal=Curr Opin Pediatr | year= 2013 | volume= 25 | issue= 6 | pages= 722-9 | pmid=24240292 | doi=10.1097/MOP.0000000000000032 | pmc=4435794 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24240292  }} </ref><ref name="pmid21079152">{{cite journal| author=Niemela JE, Lu L, Fleisher TA, Davis J, Caminha I, Natter M et al.| title=Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. | journal=Blood | year= 2011 | volume= 117 | issue= 10 | pages= 2883-6 | pmid=21079152 | doi=10.1182/blood-2010-07-295501 | pmc=3062298 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21079152  }} </ref>
*Some patients have recurrent infections with increased risk of hematologic malignancy.<ref name="pmid24240292">{{cite journal| author=Oliveira JB| title=The expanding spectrum of the autoimmune lymphoproliferative syndromes. | journal=Curr Opin Pediatr | year= 2013 | volume= 25 | issue= 6 | pages= 722-9 | pmid=24240292 | doi=10.1097/MOP.0000000000000032 | pmc=4435794 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24240292  }} </ref><ref name="pmid21079152">{{cite journal| author=Niemela JE, Lu L, Fleisher TA, Davis J, Caminha I, Natter M et al.| title=Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. | journal=Blood | year= 2011 | volume= 117 | issue= 10 | pages= 2883-6 | pmid=21079152 | doi=10.1182/blood-2010-07-295501 | pmc=3062298 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21079152  }} </ref>
*Some patients have recurrent infections with increased risk of hematologic malignancy.<ref name="pmid24240292">{{cite journal| author=Oliveira JB| title=The expanding spectrum of the autoimmune lymphoproliferative syndromes. | journal=Curr Opin Pediatr | year= 2013 | volume= 25 | issue= 6 | pages= 722-9 | pmid=24240292 | doi=10.1097/MOP.0000000000000032 | pmc=4435794 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24240292  }} </ref><ref name="pmid21079152">{{cite journal| author=Niemela JE, Lu L, Fleisher TA, Davis J, Caminha I, Natter M et al.| title=Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. | journal=Blood | year= 2011 | volume= 117 | issue= 10 | pages= 2883-6 | pmid=21079152 | doi=10.1182/blood-2010-07-295501 | pmc=3062298 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21079152  }} </ref>
===Mutated genes===
*Mutated genes involved include NRAS and [[KRAS]].
*NRAS and KRAS
 
==Cryopyrinopathy(Muckle-Wells Syndrome)==
==Cryopyrinopathy (Muckle-Wells Syndrome)==
*Caused by heterozygous mutation in the gene encoding cryopyrin (NLRP3) and the locus identified at chromosome 1q44.<ref name="pmid11687797">{{cite journal| author=Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD| title=Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. | journal=Nat Genet | year= 2001 | volume= 29 | issue= 3 | pages= 301-5 | pmid=11687797 | doi=10.1038/ng756 | pmc=4322000 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11687797  }} </ref><ref name="pmid10486324">{{cite journal| author=Cuisset L, Drenth JP, Berthelot JM, Meyrier A, Vaudour G, Watts RA et al.| title=Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44. | journal=Am J Hum Genet | year= 1999 | volume= 65 | issue= 4 | pages= 1054-9 | pmid=10486324 | doi=10.1086/302589 | pmc=1288238 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10486324  }} </ref>
*Cryopyrinopathy is caused by [[heterozygous]] mutation in the gene encoding cryopyrin (NLRP3) and the locus identified at chromosome 1q44.<ref name="pmid11687797">{{cite journal| author=Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD| title=Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. | journal=Nat Genet | year= 2001 | volume= 29 | issue= 3 | pages= 301-5 | pmid=11687797 | doi=10.1038/ng756 | pmc=4322000 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11687797  }} </ref><ref name="pmid10486324">{{cite journal| author=Cuisset L, Drenth JP, Berthelot JM, Meyrier A, Vaudour G, Watts RA et al.| title=Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44. | journal=Am J Hum Genet | year= 1999 | volume= 65 | issue= 4 | pages= 1054-9 | pmid=10486324 | doi=10.1086/302589 | pmc=1288238 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10486324  }} </ref>
*Characterized by episodic skin rash, arthralgias, and fever associated with late-onset sensorineural deafness and renal amyloidosis.<ref name="pmid11992256">{{cite journal| author=Dodé C, Le Dû N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G et al.| title=New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes. | journal=Am J Hum Genet | year= 2002 | volume= 70 | issue= 6 | pages= 1498-506 | pmid=11992256 | doi= | pmc=379138 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11992256  }} </ref>
*Characterized by episodic skin rash, [[arthralgias]], and fever associated with late-onset [[sensorineural deafness]] and [[renal amyloidosis]].<ref name="pmid11992256">{{cite journal| author=Dodé C, Le Dû N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G et al.| title=New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes. | journal=Am J Hum Genet | year= 2002 | volume= 70 | issue= 6 | pages= 1498-506 | pmid=11992256 | doi= | pmc=379138 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11992256  }} </ref>
*Limb pains emphasized on as a feature.<ref name="pmid5769632">{{cite journal| author=Black JT| title=Amyloidosis, deafness, urticaria, and limb pains: a hereditary syndrome. | journal=Ann Intern Med | year= 1969 | volume= 70 | issue= 5 | pages= 989-94 | pmid=5769632 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5769632  }} </ref>
*Limb pains emphasized on as a feature.<ref name="pmid5769632">{{cite journal| author=Black JT| title=Amyloidosis, deafness, urticaria, and limb pains: a hereditary syndrome. | journal=Ann Intern Med | year= 1969 | volume= 70 | issue= 5 | pages= 989-94 | pmid=5769632 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5769632  }} </ref>
==Hypereosinophilic Syndrome due to Somatic Mutations in STAT5b==
*Hypereosinophilic syndrome due to somatic mutations in STAT5b is characterized by [[atopic dermatitis]], [[Urticaria|urticarial]] rash, [[diarrhea]] and [[eosinophilia]]
==Chronic Mucocutaneous Candidiasis==
*Chronic mucocutaneous candidiasis includes a group of rare disorders with altered immune responses, selective against [[Candida]].<ref name="pmid12205111">{{cite journal| author=Zuccarello D, Salpietro DC, Gangemi S, Toscano V, Merlino MV, Briuglia S et al.| title=Familial chronic nail candidiasis with ICAM-1 deficiency: a new form of chronic mucocutaneous candidiasis. | journal=J Med Genet | year= 2002 | volume= 39 | issue= 9 | pages= 671-5 | pmid=12205111 | doi= | pmc=1735231 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12205111  }} </ref>
*Characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused mainly by [[Candida albicans|C''andida albicans'']].<ref name="pmid12205111">{{cite journal| author=Zuccarello D, Salpietro DC, Gangemi S, Toscano V, Merlino MV, Briuglia S et al.| title=Familial chronic nail candidiasis with ICAM-1 deficiency: a new form of chronic mucocutaneous candidiasis. | journal=J Med Genet | year= 2002 | volume= 39 | issue= 9 | pages= 671-5 | pmid=12205111 | doi= | pmc=1735231 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12205111  }} </ref>
*Can also be associated with [[Autoimmune polyendocrine syndrome|autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy]] ([[APECED]]) syndrome which is driven by mutations in [[AIRE]] ([[Autoimmunity|autoimmune]] regulator).<ref name="pmid2348835">{{cite journal| author=Ahonen P, Myllärniemi S, Sipilä I, Perheentupa J| title=Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. | journal=N Engl J Med | year= 1990 | volume= 322 | issue= 26 | pages= 1829-36 | pmid=2348835 | doi=10.1056/NEJM199006283222601 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2348835  }} </ref><ref name="pmid9398839">{{cite journal| author=Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M et al.| title=Positional cloning of the APECED gene. | journal=Nat Genet | year= 1997 | volume= 17 | issue= 4 | pages= 393-8 | pmid=9398839 | doi=10.1038/ng1297-393 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9398839  }} </ref><ref name="pmid9398840">{{cite journal| author=Finnish-German APECED Consortium| title=An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. | journal=Nat Genet | year= 1997 | volume= 17 | issue= 4 | pages= 399-403 | pmid=9398840 | doi=10.1038/ng1297-399 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9398840  }} </ref>
*High titers of neutralizing [[Autoantibody|autoantibodies]] against IL-17 and/or IL-22 are also detected.<ref name="pmid20123958">{{cite journal| author=Puel A, Döffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C et al.| title=Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. | journal=J Exp Med | year= 2010 | volume= 207 | issue= 2 | pages= 291-7 | pmid=20123958 | doi=10.1084/jem.20091983 | pmc=2822614 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20123958  }} </ref>
==Adult-Onset Immunodeficiency with Susceptibility to Mycobacteria==
*Adult-onset immunodeficiency with susceptibility to mycobacteria is a disorder predominantly found in Southeast Asians.<ref name="pmid23652167">{{cite journal| author=Chan JF, Trendell-Smith NJ, Chan JC, Hung IF, Tang BS, Cheng VC et al.| title=Reactive and infective dermatoses associated with adult-onset immunodeficiency due to anti-interferon-gamma autoantibody: Sweet's syndrome and beyond. | journal=Dermatology | year= 2013 | volume= 226 | issue= 2 | pages= 157-66 | pmid=23652167 | doi=10.1159/000347112 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23652167  }} </ref><ref name="pmid26011559">{{cite journal| author=Pithukpakorn M, Roothumnong E, Angkasekwinai N, Suktitipat B, Assawamakin A, Luangwedchakarn V et al.| title=HLA-DRB1 and HLA-DQB1 Are Associated with Adult-Onset Immunodeficiency with Acquired Anti-Interferon-Gamma Autoantibodies. | journal=PLoS One | year= 2015 | volume= 10 | issue= 5 | pages= e0128481 | pmid=26011559 | doi=10.1371/journal.pone.0128481 | pmc=4444022 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26011559  }} </ref>
*Associated with severe or disseminated infections caused by [[Nontuberculous mycobacteria|non-tuberculous mycobacteria]] and other [[Opportunistic pathogen|opportunistic pathogens]] such as [[Salmonella|non-typhoidal salmonella]], [[cytomegalovirus]], [[varicella zoster virus]], and some [[Fungus|fungi]].<ref name="pmid22913682">{{cite journal| author=Browne SK, Burbelo PD, Chetchotisakd P, Suputtamongkol Y, Kiertiburanakul S, Shaw PA et al.| title=Adult-onset immunodeficiency in Thailand and Taiwan. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 8 | pages= 725-34 | pmid=22913682 | doi=10.1056/NEJMoa1111160 | pmc=4190026 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22913682  }} </ref><ref name="pmid22403254">{{cite journal| author=Browne SK, Zaman R, Sampaio EP, Jutivorakool K, Rosen LB, Ding L et al.| title=Anti-CD20 (rituximab) therapy for anti-IFN-γ autoantibody-associated nontuberculous mycobacterial infection. | journal=Blood | year= 2012 | volume= 119 | issue= 17 | pages= 3933-9 | pmid=22403254 | doi=10.1182/blood-2011-12-395707 | pmc=3350360 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22403254  }} </ref> 
*An [[infection]] may act as an initial trigger for the production of [[Autoantibody|autoantibodies]] with repeated [[infections]] leading to increased activity.<ref name="pmid22913682">{{cite journal| author=Browne SK, Burbelo PD, Chetchotisakd P, Suputtamongkol Y, Kiertiburanakul S, Shaw PA et al.| title=Adult-onset immunodeficiency in Thailand and Taiwan. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 8 | pages= 725-34 | pmid=22913682 | doi=10.1056/NEJMoa1111160 | pmc=4190026 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22913682  }} </ref><ref name="pmid22403254">{{cite journal| author=Browne SK, Zaman R, Sampaio EP, Jutivorakool K, Rosen LB, Ding L et al.| title=Anti-CD20 (rituximab) therapy for anti-IFN-γ autoantibody-associated nontuberculous mycobacterial infection. | journal=Blood | year= 2012 | volume= 119 | issue= 17 | pages= 3933-9 | pmid=22403254 | doi=10.1182/blood-2011-12-395707 | pmc=3350360 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22403254  }} </ref>
==Recurrent Skin Infections==
*Patients with recurrent [[staphylococcal]] [[cellulitis]] and [[subcutaneous]] [[Abscess|abscesses]] have shown high titers of [[IgG|IgG1]] [[Autoantibody|autoantibodies]] against [[Interleukin 6|IL-6]], a [[Pleiotropy|pleiotropic]] [[cytokine]] released by several important cellular lineages of the skin.<ref name="pmid18097067">{{cite journal| author=Puel A, Picard C, Lorrot M, Pons C, Chrabieh M, Lorenzo L et al.| title=Recurrent staphylococcal cellulitis and subcutaneous abscesses in a child with autoantibodies against IL-6. | journal=J Immunol | year= 2008 | volume= 180 | issue= 1 | pages= 647-54 | pmid=18097067 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18097067  }} </ref><ref name="pmid8634514">{{cite journal| author=Paquet P, Piérard GE| title=Interleukin-6 and the skin. | journal=Int Arch Allergy Immunol | year= 1996 | volume= 109 | issue= 4 | pages= 308-17 | pmid=8634514 | doi=10.1159/000237257 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8634514  }} </ref>
*The [[Autoantibody|autoantibodies]] against [[Interleukin 6|IL-6]] prevent the increase in [[C-reactive protein]] ([[C-reactive protein|CRP]]) concentration during [[infection]] and the impaired [[Interleukin 6|IL-6]] mediated [[immunity]] contributes to the disease development.<ref name="pmid18097067">{{cite journal| author=Puel A, Picard C, Lorrot M, Pons C, Chrabieh M, Lorenzo L et al.| title=Recurrent staphylococcal cellulitis and subcutaneous abscesses in a child with autoantibodies against IL-6. | journal=J Immunol | year= 2008 | volume= 180 | issue= 1 | pages= 647-54 | pmid=18097067 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18097067  }} </ref>
*[[Autosomal dominant]] deficiency of signal transducer and activator of transcription 3 ([[STAT3]]) can also lead to [[cutaneous]] infections typically caused by [[Staphylococcus aureus|''Staphylococcus aureus'']].<ref name="pmid22751495">{{cite journal| author=Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L et al.| title=Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey. | journal=Medicine (Baltimore) | year= 2012 | volume= 91 | issue= 4 | pages= e1-19 | pmid=22751495 | doi=10.1097/MD.0b013e31825f95b9 | pmc=3680355 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22751495  }} </ref>
==Pulmonary Alveolar Proteinosis==
*[[Pulmonary alveolar proteinosis]] is characterized by intra-alveolar [[surfactant]] accumulation.
*A severe [[Autoimmunity|autoimmune]] disease caused by [[Autoantibody|autoantibodies]] against [[Granulocyte macrophage colony stimulating factor|granulocyte–macrophage colony-stimulating factor]] ([[Granulocyte macrophage colony stimulating factor|GM-CSF]]) resulting in impaired function of alveolar [[Macrophage|macrophages]].<ref name="pmid26077231">{{cite journal| author=Piccoli L, Campo I, Fregni CS, Rodriguez BM, Minola A, Sallusto F et al.| title=Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis. | journal=Nat Commun | year= 2015 | volume= 6 | issue=  | pages= 7375 | pmid=26077231 | doi=10.1038/ncomms8375 | pmc=4477037 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26077231  }} </ref>
*Lung [[biopsy]] shows preserved lung architecture with alveoli filled with granular, [[eosinophilic]] [[Periodic acid-Schiff stain|PAS-positive]] material with degenerating [[macrophages]].<ref name="pmid14695413">{{cite journal| author=Trapnell BC, Whitsett JA, Nakata K| title=Pulmonary alveolar proteinosis. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 26 | pages= 2527-39 | pmid=14695413 | doi=10.1056/NEJMra023226 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14695413  }} </ref>
*Hereditary [[pulmonary alveolar proteinosis]] may be caused by compound [[heterozygous]] abnormalities affecting the CSF2RA gene and CSF2 signaling, critical for [[surfactant]] [[homeostasis]] in humans.<ref name="pmid18955570">{{cite journal| author=Suzuki T, Sakagami T, Rubin BK, Nogee LM, Wood RE, Zimmerman SL et al.| title=Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. | journal=J Exp Med | year= 2008 | volume= 205 | issue= 12 | pages= 2703-10 | pmid=18955570 | doi=10.1084/jem.20080990 | pmc=2585845 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18955570  }} </ref>
*Patients with [[pulmonary alveolar proteinosis]] can also present with [[Cryptococcal Meningitis|cryptococcal meningitis]] in the setting of anti-[[Granulocyte macrophage colony stimulating factor|GM-CSF]] [[Autoantibody|autoantibodies]] as [[Granulocyte macrophage colony stimulating factor|GM-CSF]] regulates the function of [[phagocytes]] and pulmonary alveolar [[macrophages]], critical elements in [[Cryptococcus|cryptococcal]] control.<ref name="pmid29181420">{{cite journal| author=Crum-Cianflone NF, Lam PV, Ross-Walker S, Rosen LB, Holland SM| title=Autoantibodies to Granulocyte-Macrophage Colony-Stimulating Factor Associated With Severe and Unusual Manifestations of Cryptococcus gattii Infections. | journal=Open Forum Infect Dis | year= 2017 | volume= 4 | issue= 4 | pages= ofx211 | pmid=29181420 | doi=10.1093/ofid/ofx211 | pmc=5695620 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29181420  }} </ref><ref name="pmid23509356">{{cite journal| author=Rosen LB, Freeman AF, Yang LM, Jutivorakool K, Olivier KN, Angkasekwinai N et al.| title=Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis. | journal=J Immunol | year= 2013 | volume= 190 | issue= 8 | pages= 3959-66 | pmid=23509356 | doi=10.4049/jimmunol.1202526 | pmc=3675663 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23509356  }} </ref>
For more information on [[pulmonary alveolar proteinosis]], [[Pulmonary alveolar proteinosis|click here]].
==Acquired Angioedema==
*Acquired angioedema is rare disorder that causes recurrent episodes of swelling ([[edema]]) of the face or body.
*The [[edema]] can involve the lining of the [[digestive tract]] causing [[abdominal pain]] and may require unnecessary [[laparotomy]]. It can also involve the [[upper airway]], which can be life-threatening.<ref name="pmid3653633">{{cite journal| author=Weinstock LB, Kothari T, Sharma RN, Rosenfeld SI| title=Recurrent abdominal pain as the sole manifestation of hereditary angioedema in multiple family members. | journal=Gastroenterology | year= 1987 | volume= 93 | issue= 5 | pages= 1116-8 | pmid=3653633 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3653633  }} </ref><ref name="pmid8628358">{{cite journal| author=Waytes AT, Rosen FS, Frank MM| title=Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate. | journal=N Engl J Med | year= 1996 | volume= 334 | issue= 25 | pages= 1630-4 | pmid=8628358 | doi=10.1056/NEJM199606203342503 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8628358  }} </ref>
*It can occur due to the deficiency of [[C1-inhibitor|C1 inhibitor]] in the setting of [[Autoantibody|autoantibodies]] against it.<ref name="pmid3534579">{{cite journal| author=Jackson J, Sim RB, Whelan A, Feighery C| title=An IgG autoantibody which inactivates C1-inhibitor. | journal=Nature | year= 1986 | volume= 323 | issue= 6090 | pages= 722-4 | pmid=3534579 | doi=10.1038/323722a0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3534579  }} </ref><ref name="pmid3494945">{{cite journal| author=Alsenz J, Bork K, Loos M| title=Autoantibody-mediated acquired deficiency of C1 inhibitor. | journal=N Engl J Med | year= 1987 | volume= 316 | issue= 22 | pages= 1360-6 | pmid=3494945 | doi=10.1056/NEJM198705283162202 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3494945  }} </ref><ref name="pmid2454251">{{cite journal| author=Malbran A, Hammer CH, Frank MM, Fries LF| title=Acquired angioedema: observations on the mechanism of action of autoantibodies directed against C1 esterase inhibitor. | journal=J Allergy Clin Immunol | year= 1988 | volume= 81 | issue= 6 | pages= 1199-204 | pmid=2454251 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2454251  }} </ref>
*It has been associated with benign or malignant B-cell [[lymphoproliferative disorders]] such as [[chronic lymphocytic leukemia]], [[multiple myeloma]], or [[Cryoglobulinemia|essential cryoglobulinemia.]]<ref name="pmid449665">{{cite journal| author=Gelfand JA, Boss GR, Conley CL, Reinhart R, Frank MM| title=Acquired C1 esterase inhibitor deficiency and angioedema: a review. | journal=Medicine (Baltimore) | year= 1979 | volume= 58 | issue= 4 | pages= 321-8 | pmid=449665 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=449665  }} </ref>
==Atypical Hemolytic Uremic Syndrome (aHUS)==
*Atypical hemolytic uremic syndrome is a rare form of [[thrombotic microangiopathy]] that associates, in 70% of cases, with genetic or acquired disorders leading to dysregulation of the [[alternative complement pathway]].<ref name="pmid21051740">{{cite journal| author=Dragon-Durey MA, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B et al.| title=Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. | journal=J Am Soc Nephrol | year= 2010 | volume= 21 | issue= 12 | pages= 2180-7 | pmid=21051740 | doi=10.1681/ASN.2010030315 | pmc=3014031 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21051740  }} </ref>
*It can present with [[anemia]], [[thrombocytopenia]], [[hypertension]], and [[Acute kidney injury|acute renal failure]]. Renal biopsy shows a [[thrombotic microangiopathy]] and deposition of [[C3 (complement)|complement component C3]] in vessel walls.<ref name="pmid9551389">{{cite journal| author=Warwicker P, Goodship TH, Donne RL, Pirson Y, Nicholls A, Ward RM et al.| title=Genetic studies into inherited and sporadic hemolytic uremic syndrome. | journal=Kidney Int | year= 1998 | volume= 53 | issue= 4 | pages= 836-44 | pmid=9551389 | doi=10.1111/j.1523-1755.1998.00824.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9551389  }} </ref>
*[[Autoantibody|Autoantibodies]] against [[factor H]] causes at least 6% to 10% of [[Hemolytic-uremic syndrome|aHUS]] cases.<ref name="pmid21051740">{{cite journal| author=Dragon-Durey MA, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B et al.| title=Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. | journal=J Am Soc Nephrol | year= 2010 | volume= 21 | issue= 12 | pages= 2180-7 | pmid=21051740 | doi=10.1681/ASN.2010030315 | pmc=3014031 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21051740  }} </ref>
*[[Hemolytic-uremic syndrome|aHUS]] in the setting of [[antibodies]] against [[factor H]] primarily affects children between 9 and 13 years old but it also affects adults.<ref name="pmid21051740">{{cite journal| author=Dragon-Durey MA, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B et al.| title=Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. | journal=J Am Soc Nephrol | year= 2010 | volume= 21 | issue= 12 | pages= 2180-7 | pmid=21051740 | doi=10.1681/ASN.2010030315 | pmc=3014031 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21051740  }} </ref>
==Thymoma with Hypogammaglobulinemia (Good Syndrome)==
*Good syndrome is a rare acquired combined [[T cell|T-]] and [[B cell|B-cell]] [[immunodeficiency]] associated with [[thymoma]].<ref name="pmid20175853">{{cite journal| author=Hanafusa T, Umegaki N, Yamaguchi Y, Katayama I| title=Good's syndrome (hypogammaglobulinemia with thymoma) presenting intractable opportunistic infections and hyperkeratotic lichen planus. | journal=J Dermatol | year= 2010 | volume= 37 | issue= 2 | pages= 171-4 | pmid=20175853 | doi=10.1111/j.1346-8138.2009.00781.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20175853  }} </ref>
*It can present with intractable [[Opportunistic infection|opportunistic infections]], [[lichen planus]] and therapy resistant [[Diarrhea|secretory diarrhea]].<ref name="pmid20175853">{{cite journal| author=Hanafusa T, Umegaki N, Yamaguchi Y, Katayama I| title=Good's syndrome (hypogammaglobulinemia with thymoma) presenting intractable opportunistic infections and hyperkeratotic lichen planus. | journal=J Dermatol | year= 2010 | volume= 37 | issue= 2 | pages= 171-4 | pmid=20175853 | doi=10.1111/j.1346-8138.2009.00781.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20175853  }} </ref><ref name="pmid27571946">{{cite journal| author=Disselhorst MJ, Dickhoff C, Alhan C| title=Good's syndrome: an uncommon cause of therapy-resistant diarrhoea. | journal=Neth J Med | year= 2016 | volume= 74 | issue= 7 | pages= 309-12 | pmid=27571946 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27571946  }} </ref>
*Laboratory examination results indicate [[hypogammaglobulinemia]] and complete absence or decrease in the proportion of cells bearing [[B cell|B cells]] markers.<ref name="pmid20175853">{{cite journal| author=Hanafusa T, Umegaki N, Yamaguchi Y, Katayama I| title=Good's syndrome (hypogammaglobulinemia with thymoma) presenting intractable opportunistic infections and hyperkeratotic lichen planus. | journal=J Dermatol | year= 2010 | volume= 37 | issue= 2 | pages= 171-4 | pmid=20175853 | doi=10.1111/j.1346-8138.2009.00781.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20175853  }} </ref><ref name="pmid11991514">{{cite journal| author=Oshikiri T, Morikawa T, Sugiura H, Katoh H| title=Thymoma associated with hypogammaglobulinemia (Good's syndrome): report of a case. | journal=Surg Today | year= 2002 | volume= 32 | issue= 3 | pages= 264-6 | pmid=11991514 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11991514  }} </ref>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{WH}}
{{{WS}}
[[Category:Medicine]]
[[Category:Immunology]]
[[Category:Hematology]]
[[Category:Genetics]]

Latest revision as of 19:14, 23 October 2018

Immunodeficiency Main Page

Home

Overview

Classification

Immunodeficiency Affecting Cellular and Humoral Immunity

Combined Immunodeficiency

Predominantly Antibody Deficiency

Diseases of Immune Dysregulation

Congenital Defects of Phagocytes

Defects in Intrinsic and Innate Immunity

Auto-inflammatory Disorders

Complement Deficiencies

Phenocopies of Primary Immunodeficiency

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2], Ali Akram, M.B.B.S.[3], Anmol Pitliya, M.B.B.S. M.D.[4]

Overview

These disorders behave and present like primary PIDs, but they are acquired secondary to the occurrence of autoantibodies or somatic mutations.[1]These conditions are not caused by inherited genetic mutations, but instead are acquired during life.

Classification

 
 
 
 
Phenocopies of PID
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Associated with somatic mutations
 
 
 
Associated with auto-antibodies
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALPS-SFAS
 
 
 
 
Chronic mucocutaneous candidiasis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RALD (RAS-associated autoimmune leukoproliferative disease)
 
 
 
 
Adult-onset immunodeficiency with susceptibility to mycobacteria
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cryopyrinopathy (Muckle-Wells Syndrome)
 
 
 
 
Recurrent skin infections
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypereosinophilic syndrome due to somatic mutations in STAT5b
 
 
 
 
Pulmonary alveolar proteinosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acquired angioedema
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Atypical hemolytic uremic syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thymoma with hypogammaglobulinemia
 
 
 

Autoimmune Lymphoproliferative Syndrome due to Somatic FAS Mutations (ALPS-SFAS)

RAS-Associated Autoimmune Leukoproliferative Disease (RALD)

Cryopyrinopathy (Muckle-Wells Syndrome)

Hypereosinophilic Syndrome due to Somatic Mutations in STAT5b

Chronic Mucocutaneous Candidiasis

Adult-Onset Immunodeficiency with Susceptibility to Mycobacteria

Recurrent Skin Infections

Pulmonary Alveolar Proteinosis

For more information on pulmonary alveolar proteinosis, click here.

Acquired Angioedema

Atypical Hemolytic Uremic Syndrome (aHUS)

Thymoma with Hypogammaglobulinemia (Good Syndrome)

References

  1. ↑ Raje N, Dinakar C (2015). "Overview of Immunodeficiency Disorders". Immunol Allergy Clin North Am. 35 (4): 599–623. doi:10.1016/j.iac.2015.07.001. PMC 4600970. PMID 26454309.
  2. ↑ Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB; et al. (2010). "Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome". Blood. 115 (25): 5164–9. doi:10.1182/blood-2010-01-263145. PMC 2892951. PMID 20360470.
  3. ↑ Straus SE, Jaffe ES, Puck JM, Dale JK, Elkon KB, Rösen-Wolff A; et al. (2001). "The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis". Blood. 98 (1): 194–200. PMID 11418480.
  4. ↑ Sneller MC, Straus SE, Jaffe ES, Jaffe JS, Fleisher TA, Stetler-Stevenson M; et al. (1992). "A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease". J Clin Invest. 90 (2): 334–41. doi:10.1172/JCI115867. PMC 443107. PMID 1386609.
  5. ↑ Drappa J, Vaishnaw AK, Sullivan KE, Chu JL, Elkon KB (1996). "Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity". N Engl J Med. 335 (22): 1643–9. doi:10.1056/NEJM199611283352204. PMID 8929361.
  6. ↑ Canale VC, Smith CH (1967). "Chronic lymphadenopathy simulating malignant lymphoma". J Pediatr. 70 (6): 891–9. PMID 4165068.
  7. ↑ 7.0 7.1 Oliveira JB (2013). "The expanding spectrum of the autoimmune lymphoproliferative syndromes". Curr Opin Pediatr. 25 (6): 722–9. doi:10.1097/MOP.0000000000000032. PMC 4435794. PMID 24240292.
  8. ↑ 8.0 8.1 Niemela JE, Lu L, Fleisher TA, Davis J, Caminha I, Natter M; et al. (2011). "Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis". Blood. 117 (10): 2883–6. doi:10.1182/blood-2010-07-295501. PMC 3062298. PMID 21079152.
  9. ↑ Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD (2001). "Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome". Nat Genet. 29 (3): 301–5. doi:10.1038/ng756. PMC 4322000. PMID 11687797.
  10. ↑ Cuisset L, Drenth JP, Berthelot JM, Meyrier A, Vaudour G, Watts RA; et al. (1999). "Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44". Am J Hum Genet. 65 (4): 1054–9. doi:10.1086/302589. PMC 1288238. PMID 10486324.
  11. ↑ Dodé C, Le Dû N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G; et al. (2002). "New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes". Am J Hum Genet. 70 (6): 1498–506. PMC 379138. PMID 11992256.
  12. ↑ Black JT (1969). "Amyloidosis, deafness, urticaria, and limb pains: a hereditary syndrome". Ann Intern Med. 70 (5): 989–94. PMID 5769632.
  13. ↑ 13.0 13.1 Zuccarello D, Salpietro DC, Gangemi S, Toscano V, Merlino MV, Briuglia S; et al. (2002). "Familial chronic nail candidiasis with ICAM-1 deficiency: a new form of chronic mucocutaneous candidiasis". J Med Genet. 39 (9): 671–5. PMC 1735231. PMID 12205111.
  14. ↑ Ahonen P, Myllärniemi S, Sipilä I, Perheentupa J (1990). "Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients". N Engl J Med. 322 (26): 1829–36. doi:10.1056/NEJM199006283222601. PMID 2348835.
  15. ↑ Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M; et al. (1997). "Positional cloning of the APECED gene". Nat Genet. 17 (4): 393–8. doi:10.1038/ng1297-393. PMID 9398839.
  16. ↑ Finnish-German APECED Consortium (1997). "An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains". Nat Genet. 17 (4): 399–403. doi:10.1038/ng1297-399. PMID 9398840.
  17. ↑ Puel A, Döffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C; et al. (2010). "Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I." J Exp Med. 207 (2): 291–7. doi:10.1084/jem.20091983. PMC 2822614. PMID 20123958.
  18. ↑ Chan JF, Trendell-Smith NJ, Chan JC, Hung IF, Tang BS, Cheng VC; et al. (2013). "Reactive and infective dermatoses associated with adult-onset immunodeficiency due to anti-interferon-gamma autoantibody: Sweet's syndrome and beyond". Dermatology. 226 (2): 157–66. doi:10.1159/000347112. PMID 23652167.
  19. ↑ Pithukpakorn M, Roothumnong E, Angkasekwinai N, Suktitipat B, Assawamakin A, Luangwedchakarn V; et al. (2015). "HLA-DRB1 and HLA-DQB1 Are Associated with Adult-Onset Immunodeficiency with Acquired Anti-Interferon-Gamma Autoantibodies". PLoS One. 10 (5): e0128481. doi:10.1371/journal.pone.0128481. PMC 4444022. PMID 26011559.
  20. ↑ 20.0 20.1 Browne SK, Burbelo PD, Chetchotisakd P, Suputtamongkol Y, Kiertiburanakul S, Shaw PA; et al. (2012). "Adult-onset immunodeficiency in Thailand and Taiwan". N Engl J Med. 367 (8): 725–34. doi:10.1056/NEJMoa1111160. PMC 4190026. PMID 22913682.
  21. ↑ 21.0 21.1 Browne SK, Zaman R, Sampaio EP, Jutivorakool K, Rosen LB, Ding L; et al. (2012). "Anti-CD20 (rituximab) therapy for anti-IFN-γ autoantibody-associated nontuberculous mycobacterial infection". Blood. 119 (17): 3933–9. doi:10.1182/blood-2011-12-395707. PMC 3350360. PMID 22403254.
  22. ↑ 22.0 22.1 Puel A, Picard C, Lorrot M, Pons C, Chrabieh M, Lorenzo L; et al. (2008). "Recurrent staphylococcal cellulitis and subcutaneous abscesses in a child with autoantibodies against IL-6". J Immunol. 180 (1): 647–54. PMID 18097067.
  23. ↑ Paquet P, Piérard GE (1996). "Interleukin-6 and the skin". Int Arch Allergy Immunol. 109 (4): 308–17. doi:10.1159/000237257. PMID 8634514.
  24. ↑ Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L; et al. (2012). "Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey". Medicine (Baltimore). 91 (4): e1–19. doi:10.1097/MD.0b013e31825f95b9. PMC 3680355. PMID 22751495.
  25. ↑ Piccoli L, Campo I, Fregni CS, Rodriguez BM, Minola A, Sallusto F; et al. (2015). "Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis". Nat Commun. 6: 7375. doi:10.1038/ncomms8375. PMC 4477037. PMID 26077231.
  26. ↑ Trapnell BC, Whitsett JA, Nakata K (2003). "Pulmonary alveolar proteinosis". N Engl J Med. 349 (26): 2527–39. doi:10.1056/NEJMra023226. PMID 14695413.
  27. ↑ Suzuki T, Sakagami T, Rubin BK, Nogee LM, Wood RE, Zimmerman SL; et al. (2008). "Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA". J Exp Med. 205 (12): 2703–10. doi:10.1084/jem.20080990. PMC 2585845. PMID 18955570.
  28. ↑ Crum-Cianflone NF, Lam PV, Ross-Walker S, Rosen LB, Holland SM (2017). "Autoantibodies to Granulocyte-Macrophage Colony-Stimulating Factor Associated With Severe and Unusual Manifestations of Cryptococcus gattii Infections". Open Forum Infect Dis. 4 (4): ofx211. doi:10.1093/ofid/ofx211. PMC 5695620. PMID 29181420.
  29. ↑ Rosen LB, Freeman AF, Yang LM, Jutivorakool K, Olivier KN, Angkasekwinai N; et al. (2013). "Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis". J Immunol. 190 (8): 3959–66. doi:10.4049/jimmunol.1202526. PMC 3675663. PMID 23509356.
  30. ↑ Weinstock LB, Kothari T, Sharma RN, Rosenfeld SI (1987). "Recurrent abdominal pain as the sole manifestation of hereditary angioedema in multiple family members". Gastroenterology. 93 (5): 1116–8. PMID 3653633.
  31. ↑ Waytes AT, Rosen FS, Frank MM (1996). "Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate". N Engl J Med. 334 (25): 1630–4. doi:10.1056/NEJM199606203342503. PMID 8628358.
  32. ↑ Jackson J, Sim RB, Whelan A, Feighery C (1986). "An IgG autoantibody which inactivates C1-inhibitor". Nature. 323 (6090): 722–4. doi:10.1038/323722a0. PMID 3534579.
  33. ↑ Alsenz J, Bork K, Loos M (1987). "Autoantibody-mediated acquired deficiency of C1 inhibitor". N Engl J Med. 316 (22): 1360–6. doi:10.1056/NEJM198705283162202. PMID 3494945.
  34. ↑ Malbran A, Hammer CH, Frank MM, Fries LF (1988). "Acquired angioedema: observations on the mechanism of action of autoantibodies directed against C1 esterase inhibitor". J Allergy Clin Immunol. 81 (6): 1199–204. PMID 2454251.
  35. ↑ Gelfand JA, Boss GR, Conley CL, Reinhart R, Frank MM (1979). "Acquired C1 esterase inhibitor deficiency and angioedema: a review". Medicine (Baltimore). 58 (4): 321–8. PMID 449665.
  36. ↑ 36.0 36.1 36.2 Dragon-Durey MA, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B; et al. (2010). "Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome". J Am Soc Nephrol. 21 (12): 2180–7. doi:10.1681/ASN.2010030315. PMC 3014031. PMID 21051740.
  37. ↑ Warwicker P, Goodship TH, Donne RL, Pirson Y, Nicholls A, Ward RM; et al. (1998). "Genetic studies into inherited and sporadic hemolytic uremic syndrome". Kidney Int. 53 (4): 836–44. doi:10.1111/j.1523-1755.1998.00824.x. PMID 9551389.
  38. ↑ 38.0 38.1 38.2 Hanafusa T, Umegaki N, Yamaguchi Y, Katayama I (2010). "Good's syndrome (hypogammaglobulinemia with thymoma) presenting intractable opportunistic infections and hyperkeratotic lichen planus". J Dermatol. 37 (2): 171–4. doi:10.1111/j.1346-8138.2009.00781.x. PMID 20175853.
  39. ↑ Disselhorst MJ, Dickhoff C, Alhan C (2016). "Good's syndrome: an uncommon cause of therapy-resistant diarrhoea". Neth J Med. 74 (7): 309–12. PMID 27571946.
  40. ↑ Oshikiri T, Morikawa T, Sugiura H, Katoh H (2002). "Thymoma associated with hypogammaglobulinemia (Good's syndrome): report of a case". Surg Today. 32 (3): 264–6. PMID 11991514.

Template:WH {Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Phenocopies_of_primary_immunodeficiency&oldid=1499443"