title: Update on the hyper immunoglobulin M syndromes.
abstract: The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination (CSR), with or without defects of somatic hypermutation (SHM). They can be classified as defects of signalling through CD40 causing both a humoral immunodeficiency and a susceptibility to opportunistic infections, or intrinsic defects in B cells of the mechanism of CSR resulting in a pure humoral immunodeficiency. A HIGM picture can also be seen as part of generalized defects of DNA repair and in antibody deficiency syndromes, such as common variable immunodeficiency. CD40 signalling defects may require corrective therapy with bone marrow transplantation. Gene therapy, a potential curative approach in the future, currently remains a distant prospect. Those with a defective CSR mechanism generally do well on immunoglobulin replacement therapy. Complications may include autoimmunity, lymphoid hyperplasia and, in some cases, a predisposition to lymphoid malignancy.
authors.affiliation: Centre for Immunodeficiency, Institute of Child Health, London, UK. davieg1@gosh.nhs.uk
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000172:deficiency; D023201:CD40 Ligand / Q000172:deficiency; D002454:Cell Differentiation / Q000276:immunology; D004260:DNA Repair; D004476:Ectodermal Dysplasia / Q000235:genetics / Q000276:immunology; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D017578:Immunoglobulin Class Switching / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand