Phenotypic and clinical heterogeneity associated with monoallelic TNFRSF13B−A181E mutations in common variable immunodeficiency

Abstract

Mutations in the TNFRSF13B ( TACI) gene have been reported to be associated with Common Variable ImmunoDeficiency (CVID). Of 48 patients evaluated within the immunodeficiency clinic, 39 had CVID, 6 had symptomatic IgA deficiency (IgAD) with or without IgG2 and IgG4 subclass deficiency, while 3 had unclassified immune dysregulatory disorders. In all 48 patients TACI genetic testing was performed, and monoallelic mutations were observed in 4 of the 39 CVID patients (10.26%), an incidence comparable to other studies. Of the 6 IgAD patients, 1 had a heterozygous TACI mutation (16.67%), while of the 3 unclassified patients, 1 had a monoallelic TACI mutation (33.3%), but his sibling who also had the same mutation had CVID. The A181E mutation is one of the statistically significant, among the known TACI gene mutations. Here, 5 of the 6 patients were found to have the A181E mutation (10.42%), which is higher than previously observed. We also evaluated 114 controls and found the A181E mutation in only 1 individual (0.88%). We report in this study that the A181E mutation is associated with a very heterogeneous clinical presentation along with variability in B-cell numbers and amount of TACI protein on memory B cells.