Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Allergy Clin Immunol. 2007 Nov;120(5):1178-85.

Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes.

Author information

  • 1Department of Medicine, Pediatrics and the Immunobiology Center, Mount Sinai Medical School, New York, NY, USA.

Abstract

BACKGROUND:

Mutations in the gene coding for transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) have been identified in common variable immunodeficiency (CVID). Mutations coincided with immunodeficiency in families, suggesting dominant inheritance.

OBJECTIVE:

Because most subjects with CVID have no immunodeficient family members and heterozygous mutations predominate, the role of TACI mutations in sporadic CVID is unclear.

METHODS:

TACI was sequenced from the genomic DNA of 176 subjects with CVID and family members. B cells of subjects with or without mutations were examined for binding to the ligand, a proliferation inducing ligand (APRIL), and for proliferation and immunoglobulin production after ligand stimulation. Data analysis was performed to assess the clinical relevance of TACI mutations.

RESULTS:

Heterozygous TACI mutations were found in 13 subjects (7.3%). Six with mutations (46%) had episodes of autoimmune thrombocytopenia, in contrast with 12% of 163 subjects without mutations; splenomegaly and splenectomy were significantly increased (P = .012; P = .001.) B cells of some had impaired binding of APRIL and on culture with this ligand were defective in proliferation and immunoglobulin production; however, this was not different from B cells of subjects without mutations. Eight first-degree relatives from 5 families had the same mutations but were not immune-deficient, and their B cells produced normal amounts of IgG and IgA after APRIL stimulation.

CONCLUSION:

Mutations in TACI significantly predispose to autoimmunity and lymphoid hyperplasia in CVID, but additional genetic or environmental factors are required to induce immune deficiency.

CLINICAL IMPLICATIONS:

Additional causes of this common immune deficiency syndrome remain to be determined.

PMID:
17983875
[PubMed - indexed for MEDLINE]
PMCID:
PMC2908504
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk