Poon, E; (2006) Mutation detection in TNFRSF13b encoding taci in patients with common variable immunodeficency. Doctoral thesis , UCL (University College London).

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Abstract

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterised by defects in immunoglobulin production and function. The molecular basis of CVID is not clear but a number of genes have recently been implicated. The TNF receptor superfamily member transmembrane activator and CAML interactor (TACI) is part of the APRIL-BAFF-BAFFR-BCMA-TACI system. It plays an essential role in the humoral immunity especially in the maturation, proliferation and differentiation of B cells in human and mice. Recent reports suggest that mutations in TACI could form the molecular cause of a subset of patients with CVID. Multiplex capillary heteroduplex analysis, a mutation screening technique, was coupled with direct sequencing to analyse all five exons in TACI gene in a cohort of 26 CVID patients and in 47 healthy controls. The use of this screening strategy allowed high through-put analysis of samples with low cost but still achieved a high level of sensitivity. Through this approach, 2 individuals with CVID were identified with a heterozygous mutation that causes a functionally deleterious amino acid substitution, C104R, in TACI. To study the functional consequences of heterozygous C104R change, a lentiviral expression system was chosen to express mutant TACI in heterologous cell lines and B cell lines. TACI cDNA containing the C104R mutation was cloned into a lentiviral transfer vector.

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