In conclusion, pathogenic stop variants in the ARD of NFKB2 can cause 'infection-only' CVID with an abnormal B-cell phenotype and a variable clinical penetrance.
TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) mutations seem to be associated with autoimmunity and common variable immunodeficiency in humans.
TNFRSF13B hemizygosity does not recapitulate autoimmune features of CVID-associated C104R and A181ETNFRSF13B mutations, which likely encode dominant negative products, but instead reveals selective TACI haploinsufficiency at later stages of B-cell development.
Remarkably, we did not find the TNFRSF13B mutation in the third index-child with CVID, despite his hypogammaglobulinaemia and decreased response to unconjugated pneumococcal vaccine.
In some patients with common variable immunodeficiency (CVID) and immunoglobulin (Ig) A deficiency (IgAD), tumor necrosis factor (TNF) family receptor transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) gene mutations have been reported.
Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes.
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.
To summarize the recent advancements in common variable immune deficiency (CVID), specifically CVID genetics, clinical discoveries and treatment implications.
Moreover, splenomegaly was associated with higher TACI expression, suggesting that perturbations of TACI function may underlie lymphoproliferation in CVID.
We report the case of a man with CVID in association with a heterozygous TACI gene mutation (C104R) who had a highly unusual, invasive, polyclonal CD8+ T-cell lymphoproliferation resulting in massive hepatosplenomegaly and causing renal impairment because of infiltration.
The hypothesis that the CVID gene predisposes heterozygous female carriers to cancer may be evaluated more easily in the future when the genetic basis for CVID is better understood.
Mutations in TNFRSF13B, the gene encoding transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI), are found in 10% of patients with common variable immunodeficiency.