Qamar Nashmia, Fuleihan Ramsay L
Division of Allergy and Immunology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Clin Rev Allergy Immunol. 2014 Apr;46(2):120-30. doi: 10.1007/s12016-013-8378-7.
The hyper IgM syndromes are a group of rare inherited immune deficiency disorders characterized by impairment of immunoglobulin isotype switching resulting from defects in the CD40 ligand/CD40 signaling pathway. X-linked forms of hyper IgM are caused by defects in the CD40 ligand gene or NF-κB essential modulator, while autosomal recessive forms of hyper IgM are caused by defects in CD40 or downstream signaling molecules including activation-induced cytidine deaminase, uracil N glycosylase or postmeiotic segregation increased 2. The loss of interaction between CD40 and its ligand 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 defects of sinaling molecules downstream of CD40 with the exception of defects of the NF-κB complex, which mediates signaling via multiple receptor pathways. With many genetic defects in the hyper IgM syndrome identified, it is possible to diagnose patients definitively, to perform genetic screening, and to delineate the clinical manifestations of the different diseases in this syndrome. Stem cell transplantation is an available therapeutic option for defects that result in a combined immunodeficiency while antibody replacement appears sufficient for the strictly humoral immunodeficiencies.
高IgM综合征是一组罕见的遗传性免疫缺陷疾病，其特征是由于CD40配体/CD40信号通路缺陷导致免疫球蛋白同种型转换受损。X连锁型高IgM是由CD40配体基因或NF-κB必需调节因子缺陷引起的，而常染色体隐性型高IgM是由CD40或下游信号分子缺陷引起的，包括活化诱导的胞苷脱氨酶、尿嘧啶N糖苷酶或减数分裂后分离增加2。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，而除了通过多种受体途径介导信号传导的NF-κB复合物缺陷外，CD40下游信号分子缺陷似乎仅影响B细胞分化。随着高IgM综合征中许多遗传缺陷的确定，有可能对患者进行明确诊断、进行基因筛查，并描绘该综合征中不同疾病的临床表现。干细胞移植是导致联合免疫缺陷的缺陷的一种可用治疗选择，而抗体替代似乎足以治疗严格的体液免疫缺陷。
