Etzioni Amos, Ochs Hans D
Department of Pediatrics, Meyer Children's Hospital, B. Rappaport Faculty of Medicine, Technion, Haifa, Israel 31096.
Pediatr Res. 2004 Oct;56(4):519-25. doi: 10.1203/01.PDR.0000139318.65842.4A. Epub 2004 Aug 19.
The hyper IgM syndromes (HIGM) are a group of primary immune deficiency disorders characterized by defective CD40 signaling by B cells affecting class switch recombination and somatic hypermutation. As a consequence, patients with HIGM have decreased concentrations of serum IgG and IgA and normal or elevated IgM, leading to increased susceptibility to infections. The most common HIGM syndrome is X-linked and due to mutations of CD40 ligand (CD40L) expressed by activated CD4(+) T lymphocytes. Four other genes, expressed by B cells, have been associated with the HIGM phenotype. Mutations of CD40, the receptor for CD40L, cause a rare autosomal form of HIGM with a clinical phenotype similar to CD40L deficiency. Mutations of Activation-Induced Cytidine Deaminase (AICDA) and Uracil (DNA) Glycosylase (UNG), both expressed by follicular B lymphocytes, lead to defective class switch recombination and somatic hypermutation. Mutations of Nuclear Factor kappa B Essential Modulator (NEMO), an X-chromosome associated gene, result in hypohidrotic ectodermal dysplasia and immune deficiency. Thus, the molecular definition of these rare primary immune deficiency disorders has shed light on the complex events leading to the production of high-affinity, antigen-specific antibodies of different isotypes.
高IgM综合征（HIGM）是一组原发性免疫缺陷疾病，其特征是B细胞的CD40信号传导缺陷，影响类别转换重组和体细胞超突变。因此，HIGM患者血清IgG和IgA浓度降低，IgM正常或升高，导致感染易感性增加。最常见的HIGM综合征是X连锁的，由活化的CD4(+) T淋巴细胞表达的CD40配体（CD40L）突变引起。另外四个由B细胞表达的基因与HIGM表型相关。CD40L的受体CD40突变导致一种罕见的常染色体形式的HIGM，其临床表型与CD40L缺乏相似。滤泡B淋巴细胞表达的活化诱导胞苷脱氨酶（AICDA）和尿嘧啶（DNA）糖基化酶（UNG）突变导致类别转换重组和体细胞超突变缺陷。X染色体相关基因核因子κB必需调节因子（NEMO）突变导致少汗性外胚层发育不良和免疫缺陷。因此，这些罕见的原发性免疫缺陷疾病的分子定义揭示了导致产生不同同种型高亲和力、抗原特异性抗体的复杂事件。
