| 초록 |
Hyper immunoglobulin M syndrome (HIGM) is a term used to describe a heterogeneous group of disorders characterized by normal or elevated concentrations of serum IgM but markedly decreased IgG, IgA, and IgE. This immunological phenotype is largely due to the failure of B cells to complete their maturational program by undergoing immunoglobulin-isotype class switch recombination and somatic hypermutation. The most common syndrome is X-linked and due to mutations of the CD154 (CD40L) gene, which encodes for the CD40 ligand molecule expressed transiently on the surface of activated T cells. Four other genes, expressed by B cells, have been associated with the HIGM phenotype. Mutations in the CD40 gene cause a rare autosomal form of HIGM with a clinical phenotype similar to CD154 deficiency. Mutations in the activation-induced cytidine deaminase gene and the uracil DNA glycosylase gene lead to defective class switch recombination and somatic hypermutation. Mutations in the nuclear factor kappa B essential modulator gene have been identified as the cause of another type of X-linked HIGM associated with hypohidrotic ectodermal dysplasia. The recent delineation of the different HIGMs has provided much information on the mechanisms underlying antibody maturation. |
