Autoimmunity in Hyper-IgM Syndrome
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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.
Results and discussions
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.
KeywordsAutoimmunity CD40 CD40L hyper IgM inflammatory bowel disease
- 7.Facchetti F, Appiani C, Salvi L, Levy J, Notarangelo LD. Immunohistologic analysis of ineffective CD40–CD40 ligand interaction in lymphoid tissues from patients with X-linked immunodeficiency with hyper-IgM. Abortive germinal center cell reaction and severe depletion of follicular dendritic cells. J Immunol 1995;154:6624–33.PubMedGoogle Scholar
- 23.Quartier P, Bustamante J, Sanal O, Plebani A, Debré M, Deville A, et al. Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to activation-induced cytidine deaminase deficiency. Clin Immunol 2004;110:22–9. Erratum in: Clin Immunol. 113:220, 2004.PubMedCrossRefGoogle Scholar