Autoimmunity in Hyper-IgM Syndrome
- 2 February 2008
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Clinical Immunology
- Vol. 28 (S1), 62-66
- https://doi.org/10.1007/s10875-008-9171-x
Abstract
Immunodeficiency with hyper-IgM (HIGM) results from genetic defects in the CD40–CD40 ligand (CD40L) pathway or in the enzymes required for immunoglobulin class switch recombination and somatic hypermutation. HIGM can thus be associated with an impairment of both B-cell and T-cell activation. There are seven main subtypes of HIGM and the most frequent is X-linked HIGM, resulting from CD40L mutations. In addition to the susceptibility to recurrent and opportunistic infections, these patients are prone to autoimmune manifestations, especially hematologic abnormalities, arthritis, and inflammatory bowel disease. Furthermore, organ-specific autoantibodies are commonly found in HIGM patients. The mechanisms by which HIGM associates to autoimmunity are not completely elucidated but a defective development of regulatory T cells, the presence of IgM autoantibodies and an impaired peripheral B-cell tolerance checkpoint have been implicated. This article reviews the main subtypes of HIGM syndrome, the clinical autoimmune manifestations found in these patients, and the possible mechanisms that would explain this association.This publication has 31 references indexed in Scilit:
- Immunodeficiency and Autoimmune Phenomena in Female Hyper‐IgM SyndromeAnnals of the New York Academy of Sciences, 2007
- CD40 ligand and MHC class II expression are essential for human peripheral B cell toleranceThe Journal of Experimental Medicine, 2007
- Hyper-immunoglobulin M syndrome caused by a mutation in the promotor for CD40LImmunology, 2007
- Hyper-IgM syndromesCurrent Opinion in Rheumatology, 2006
- Hyper‐immunoglobulin M syndromes caused by intrinsic B‐lymphocyte defectsImmunological Reviews, 2005
- Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological featuresImmunological Reviews, 2005
- Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to Activation-Induced Cytidine Deaminase deficiencyClinical Immunology, 2004
- Activation-Induced Cytidine Deaminase (AID) Deficiency Causes the Autosomal Recessive Form of the Hyper-IgM Syndrome (HIGM2)Cell, 2000
- Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production.JCI Insight, 1996
- A novel function of CD40: induction of cell death in transformed cells.The Journal of Experimental Medicine, 1996