Functional analysis of transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) mutations associated with common variable immunodeficiency.

摘要

Mutations in TNFRSF13B, the gene encoding the transmem-brane activator and calcium-modulating cyclophilin ligand inter-actor (TACI), have been identified in 5% to 10% of patients with common variable immunodeficiency (CVID).1'2 The most common TACI variants in patients with CVID are C104R in the ligand-binding cysteine-rich domain 2 (CRD2) and A181E in the transmembrane domain of TACI. Each is found in the heterozygous state in 2% to 5% of patients with CVID but also in 0.5% to 1% of healthy subjects.1"3 Both destroy the capacity of TACI ligation to activate nuclear factor kB (NF-kB). We have examined the function of TACI coding variants that have been described in patients with CVID and their relatives but thus far not in healthy subjects.