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Impaired Ig class switch recombination

MedGen UID:
374953
Concept ID:
C1842528
Finding
Synonyms: Impaired Ig class switch recombination (CSR); Impaired Ig class-switch recombination (CSR)
 
HPO: HP:0002959

Definition

An impairment of the class-switch recombination process that normally leads B lymphocytes to produce IgG, IgA, or IgE. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVImpaired Ig class switch recombination

Conditions with this feature

Hyper-IgM syndrome type 1
MedGen UID:
96019
Concept ID:
C0398689
Disease or Syndrome
X-linked hyper IgM syndrome (HIGM1), a disorder of abnormal T- and B-cell function, is characterized by low serum concentrations of IgG, IgA, and IgE with normal or elevated serum concentrations of IgM. Mitogen proliferation may be normal, but NK- and T-cell cytotoxicity can be impaired. Antigen-specific responses are usually decreased or absent. Total numbers of B cells are normal but there is a marked reduction of class-switched memory B cells. Defective oxidative burst of both neutrophils and macrophages has been reported. The range of clinical findings varies, even within the same family. More than 50% of males with HIGM1 develop symptoms by age one year, and more than 90% are symptomatic by age four years. HIGM1 usually presents in infancy with recurrent upper- and lower-respiratory tract bacterial infections, opportunistic infections including Pneumocystis jirovecii pneumonia, and recurrent or protracted diarrhea that can be infectious or noninfectious and is associated with failure to thrive. Neutropenia is common; thrombocytopenia and anemia are less commonly seen. Autoimmune and/or inflammatory disorders (such as sclerosing cholangitis) as well as increased risk for neoplasms have been reported as medical complications of this disorder. Significant neurologic complications, often the result of a CNS infection, are seen in 5%-15% of affected males. Liver disease, a serious complication of HIGM1 once observed in more than 80% of affected males by age 20 years, may be decreasing with adequate screening and treatment of Cryptosporidium infection.
Hyper-IgM syndrome type 2
MedGen UID:
354548
Concept ID:
C1720956
Disease or Syndrome
Hyper-IgM syndrome type 2 (HIGM2) is a rare immunodeficiency characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
Hyper-IgM syndrome type 3
MedGen UID:
328419
Concept ID:
C1720957
Disease or Syndrome
Type 3 immunodeficiency with hyper-IgM (HIGM3), first described in humans by Ferrari et al. (2001), is characterized by hypogammaglobulinemia with normal or elevated levels of IgM. For a general phenotypic description and a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
Hyper-IgM syndrome type 5
MedGen UID:
328420
Concept ID:
C1720958
Disease or Syndrome
Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
Hyper-IgM syndrome type 4
MedGen UID:
330847
Concept ID:
C1842413
Disease or Syndrome
Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process (summary by Imai et al., 2003). For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).

Recent clinical studies

Etiology

Farnsworth CW, Schott EM, Benvie A, Kates SL, Schwarz EM, Gill SR, Zuscik MJ, Mooney RA
J Immunol 2018 Jul 15;201(2):560-572. Epub 2018 Jun 1 doi: 10.4049/jimmunol.1800253. PMID: 29858265Free PMC Article
Longerich S, Orelli BJ, Martin RW, Bishop DK, Storb U
DNA Repair (Amst) 2008 Feb 1;7(2):253-66. Epub 2007 Nov 26 doi: 10.1016/j.dnarep.2007.10.002. PMID: 18036997Free PMC Article

Diagnosis

Husain A, Xu J, Fujii H, Nakata M, Kobayashi M, Wang JY, Rehwinkel J, Honjo T, Begum NA
EMBO J 2020 Aug 3;39(15):e102931. Epub 2020 Jun 8 doi: 10.15252/embj.2019102931. PMID: 32511795Free PMC Article
Schena F, Volpi S, Faliti CE, Penco F, Santi S, Proietti M, Schenk U, Damonte G, Salis A, Bellotti M, Fais F, Tenca C, Gattorno M, Eibel H, Rizzi M, Warnatz K, Idzko M, Ayata CK, Rakhmanov M, Galli T, Martini A, Canossa M, Grassi F, Traggiai E
Cell Rep 2013 Jun 27;3(6):1824-31. Epub 2013 Jun 13 doi: 10.1016/j.celrep.2013.05.022. PMID: 23770243
Durandy A, Kracker S
Arthritis Res Ther 2012 Jul 30;14(4):218. doi: 10.1186/ar3904. PMID: 22894609Free PMC Article
He B, Qiao X, Klasse PJ, Chiu A, Chadburn A, Knowles DM, Moore JP, Cerutti A
J Immunol 2006 Apr 1;176(7):3931-41. doi: 10.4049/jimmunol.176.7.3931. PMID: 16547227

Therapy

He L, Peng X, Chen Y, Liu G, Liu Z, Zhu J, Liu Y, Liu H, Liang Y, Liu F, Sun L, Peng Y
Am J Nephrol 2016;43(3):179-94. Epub 2016 Apr 14 doi: 10.1159/000445697. PMID: 27073891

Clinical prediction guides

Tamrakar A, Kodgire P
Mol Immunol 2022 Feb;142:37-49. Epub 2021 Dec 24 doi: 10.1016/j.molimm.2021.12.014. PMID: 34959071
Björkman A, Du L, Felgentreff K, Rosner C, Pankaj Kamdar R, Kokaraki G, Matsumoto Y, Davies EG, van der Burg M, Notarangelo LD, Hammarström L, Pan-Hammarström Q
J Immunol 2015 Dec 15;195(12):5608-15. Epub 2015 Nov 6 doi: 10.4049/jimmunol.1501633. PMID: 26546606
Kracker S, Imai K, Gardès P, Ochs HD, Fischer A, Durandy AH
Proc Natl Acad Sci U S A 2010 Dec 21;107(51):22225-30. Epub 2010 Dec 6 doi: 10.1073/pnas.1012591108. PMID: 21135220Free PMC Article
Sekine H, Ferreira RC, Pan-Hammarström Q, Graham RR, Ziemba B, de Vries SS, Liu J, Hippen K, Koeuth T, Ortmann W, Iwahori A, Elliott MK, Offer S, Skon C, Du L, Novitzke J, Lee AT, Zhao N, Tompkins JD, Altshuler D, Gregersen PK, Cunningham-Rundles C, Harris RS, Her C, Nelson DL, Hammarström L, Gilkeson GS, Behrens TW
Proc Natl Acad Sci U S A 2007 Apr 24;104(17):7193-8. Epub 2007 Apr 4 doi: 10.1073/pnas.0700815104. PMID: 17409188Free PMC Article
Imai K, Catalan N, Plebani A, Maródi L, Sanal O, Kumaki S, Nagendran V, Wood P, Glastre C, Sarrot-Reynauld F, Hermine O, Forveille M, Revy P, Fischer A, Durandy A
J Clin Invest 2003 Jul;112(1):136-42. doi: 10.1172/JCI18161. PMID: 12840068Free PMC Article

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