Fuleihan R L
Department of Pediatrics, Yale Child Health Research Center, Yale University School of Medicine, POB 208081, New Haven, CT 06520-8081, USA.
Curr Allergy Asthma Rep. 2001 Sep;1(5):445-50. doi: 10.1007/s11882-001-0030-6.
The hyper IgM syndrome is a rare, inherited immune deficiency disorder resulting from defects in the CD40 ligand/CD40-signaling pathway. X-linked hyper IgM is caused by defects in the CD40 ligand gene, while autosomal recessive hyper IgM is caused by defects in the CD40-activated RNA-editing enzyme, activation-induced cytidine deaminase, which is required for immunoglobulin isotype switching and somatic hypermutation in B cells. The loss of interaction between CD40 and its ligand in X-linked hyper IgM results in an impairment of T cell function, of B cell differentiation, and of monocyte function, while only B cell differentiation appears to be affected in autosomal recessive hyper IgM. With genetic defects in the hyper IgM syndrome identified, it is possible to diagnose patients definitely, to perform genetic screening, and to delineate the clinical manifestations of this syndrome. Further research may lead to novel and definitive therapeutic options for patients with hyper IgM syndrome.
高IgM综合征是一种罕见的遗传性免疫缺陷疾病，由CD40配体/CD40信号通路缺陷引起。X连锁高IgM是由CD40配体基因缺陷所致，而常染色体隐性高IgM则是由CD40激活的RNA编辑酶（即激活诱导的胞苷脱氨酶）缺陷引起，该酶是B细胞免疫球蛋白同种型转换和体细胞超突变所必需的。在X连锁高IgM中，CD40与其配体之间相互作用的丧失导致T细胞功能、B细胞分化和单核细胞功能受损，而在常染色体隐性高IgM中似乎仅B细胞分化受到影响。随着高IgM综合征基因缺陷的明确，有可能对患者进行确切诊断、进行基因筛查并明确该综合征的临床表现。进一步的研究可能会为高IgM综合征患者带来新的、确切的治疗选择。
