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

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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.

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Acknowledgments

We thank the family for participating in this study for the benefit of others. We acknowledge the ADHB management for their support. This study is supported by the A + Charitable Trust and the Immune Deficiencies Foundation of New Zealand (IDFNZ). We thank Drs Maia Brewerton, Shannon Brothers and Anthony Jordan for their helpful discussions.

Author information

Authors and Affiliations

  1. Department of Virology and Immunology, Auckland City Hospital, Park Rd, Auckland, New Zealand

    Wikke Koopmans, See-Tarn Woon & Rohan Ameratunga

  2. Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand

    Wikke Koopmans, See-Tarn Woon, Peter Browett & Rohan Ameratunga

  3. Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand

    Anna E. S. Brooks & P. Rod Dunbar

  4. School of Biological Sciences, University of Auckland, Auckland, New Zealand

    Anna E. S. Brooks & P. Rod Dunbar

  5. Department of Clinical Immunology, Auckland City Hospital, Park Rd, Auckland, New Zealand

    Rohan Ameratunga

Authors
  1. Wikke Koopmans
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  2. See-Tarn Woon
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Corresponding author

Correspondence to Rohan Ameratunga.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplement Table I

B cell populations in family members and healthy controls. (DOC 39 kb)

Supplement Table II

In vivo vaccine responses of II.2 and II.3. (DOC 40 kb)

Supplement Table III

Mitogen-induced lymphocyte proliferation. (DOC 36 kb)

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Koopmans, W., Woon, ST., Brooks, A.E.S. et al. Clinical Variability of Family Members with the C104R Mutation in Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor (TACI). J Clin Immunol 33, 68–73 (2013). https://doi.org/10.1007/s10875-012-9793-x

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  • DOI: https://doi.org/10.1007/s10875-012-9793-x

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