Prospects for modulating the CD40/CD40L pathway in the therapy of the hyper-IgM syndrome:

Innate Immunity

XiangxueMeng¹ 

关键词: Hyper-IgM (HIGM) syndrome;    CD40/CD40L pathway;    immunoglobulin-isotype class switch recombination (CSR);    somatic hypermutation (SHM);    genetic defects;   

DOI  :  10.1177/1753425917739681

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

The critical role of the CD40/CD40L pathway in B-cell proliferation, immunoglobulin (Ig) isotype switching and germinal center formation has been studied and described extensively in previous literature. Interruption of the CD40/CD40L signal causes hyper-IgM (HIGM) syndrome, which has been classified and recognized as a group of rare inherited immune deficiency disorders. Defects in CD40 and CD40L interactions or in downstream signaling molecules, including activation-induced cytidine deaminase, uracyl-DNA-glycosylase, NF-κB and DNA repair enzymes, result in an increased level of serum IgM and a significantly decreased or absent level of IgA, IgG and IgE that is accompanied by severe recurrent infections and autoimmune diseases. Many genetic defects in HIGM have been identified and, as a result, it is possible for patients to be definitively diagnosed by gene sequencing and to delineate the immunological features of the patients. Modifying the CD40/CD40L signaling pathway may offer the possibility of rest...

【 授权许可】

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