Journal of Clinical Immunology

, Volume 33, Issue 1, pp 68–73

Clinical Variability of Family Members with the C104R Mutation in Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor (TACI)

  • Wikke Koopmans
  • See-Tarn Woon
  • Anna E. S. Brooks
  • P. Rod Dunbar
  • Peter Browett
  • Rohan Ameratunga
Original Research

DOI: 10.1007/s10875-012-9793-x

Cite this article as:
Koopmans, W., Woon, ST., Brooks, A.E.S. et al. J Clin Immunol (2013) 33: 68. doi:10.1007/s10875-012-9793-x

Abstract

Purpose

Common Variable Immunodeficiency Disorder (CVID) is a complex disorder that predisposes patients to recurrent and severe infections. The C104R mutation in the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is the most frequent mutation identified in patients with CVID. We carried out a detailed immunological and molecular study in a family with a C104R mutation.

Methods

We have undertaken segregation analysis of a kindred with C104R mutations of the TACI gene. Detailed immunological and molecular investigations were carried out for this kindred and the clinical phenotype was compared to the genotype.

Results

Segregation analysis of our kindred showed that inheriting single or double copy of the C104R mutation does not consign an individual to CVID. All heterozygotes in the family were phenotypically different, ranging from asymptomatic to ill-health. A family member with a wild type TACI variant had CVID-related phenotype including IgA deficiency and type 1 diabetes. Interestingly, a family member with the homozygous C104R/C104R variant did not meet the criteria for CVID because he had excellent, albeit unsustained, vaccine responses to T cell dependent and T cell independent vaccine antigens despite profound hypogammaglobulinemia.

Conclusion

The C104R mutation does not correlate with the clinical phenotypes in this family.

Keywords

CVID C104R mutation infection TACI 

Supplementary material

10875_2012_9793_MOESM1_ESM.doc (39 kb)
Supplement Table IB cell populations in family members and healthy controls. (DOC 39 kb)
10875_2012_9793_MOESM2_ESM.doc (40 kb)
Supplement Table IIIn vivo vaccine responses of II.2 and II.3. (DOC 40 kb)
10875_2012_9793_MOESM3_ESM.doc (36 kb)
Supplement Table IIIMitogen-induced lymphocyte proliferation. (DOC 36 kb)

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Wikke Koopmans
    • 1
    • 2
  • See-Tarn Woon
    • 1
    • 2
  • Anna E. S. Brooks
    • 3
    • 4
  • P. Rod Dunbar
    • 3
    • 4
  • Peter Browett
    • 2
  • Rohan Ameratunga
    • 1
    • 2
    • 5
  1. 1.Department of Virology and ImmunologyAuckland City HospitalAucklandNew Zealand
  2. 2.Department of Molecular Medicine and PathologyUniversity of AucklandAucklandNew Zealand
  3. 3.Maurice Wilkins CentreUniversity of AucklandAucklandNew Zealand
  4. 4.School of Biological SciencesUniversity of AucklandAucklandNew Zealand
  5. 5.Department of Clinical ImmunologyAuckland City HospitalAucklandNew Zealand

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