Journal of Clinical Immunology

, 29:777

Novel Mutations in TACI (TNFRSF13B) Causing Common Variable Immunodeficiency

  • Javad Mohammadi
  • Chonghai Liu
  • Asghar Aghamohammadi
  • Astrid Bergbreiter
  • Likun Du
  • Jiayi Lu
  • Nima Rezaei
  • Ali Akbar Amirzargar
  • Mostafa Moin
  • Ulrich Salzer
  • Qiang Pan-Hammarström
  • Lennart Hammarström
Article

DOI: 10.1007/s10875-009-9317-5

Cite this article as:
Mohammadi, J., Liu, C., Aghamohammadi, A. et al. J Clin Immunol (2009) 29: 777. doi:10.1007/s10875-009-9317-5

Abstract

Introduction

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production. The disorder is also characterized by co-occurrence of autoimmune, lymphoproliferative, and granulomatous diseases. Mutations in the gene encoding TACI (Transmembrane Activator and CAML Interactor, TNFRSF13B) were previously found to be associated with CVID.

Materials and Methods

We therefore sequenced TNFRSF13B gene in a cohort of 48 Iranian CVID patients. Expression of TACI and binding of A proliferation-inducing ligand (APRIL) were tested by FACS.

Results

We identified one patient with a homozygous G to T substitution in the TNFRSF13B gene at the splice site of intron 1 (c.61+1G>T), which abolished expression of the TACI molecule and binding capacity of APRIL. This represents the second CVID patient in the world with a complete absence of TACI expression. B cell lines from family members carrying the same mutation in a heterozygous form showed a reduced level of TACI expression and APRIL-binding capacity, suggesting a gene dosage effect. In addition, we found the previously recognized C104R and C172Y mutations in a heterozygous form in two patients with CVID and one, novel, heterozygous P42T mutation.

Conclusion

TACI mutations were observed in Iran CVID patients in a similar frequency as in other Caucasian populations. The novel mutations identified in this study support the notion of a crucial role for TACI in B cell differentiation.

Keywords

Common variable immunodeficiencyTACIhumanimmunoglobulinsmutation

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Javad Mohammadi
    • 1
  • Chonghai Liu
    • 1
  • Asghar Aghamohammadi
    • 2
  • Astrid Bergbreiter
    • 4
  • Likun Du
    • 1
  • Jiayi Lu
    • 1
  • Nima Rezaei
    • 2
  • Ali Akbar Amirzargar
    • 5
  • Mostafa Moin
    • 3
  • Ulrich Salzer
    • 4
  • Qiang Pan-Hammarström
    • 1
  • Lennart Hammarström
    • 1
  1. 1.Division of Clinical Immunology, Department of Laboratory MedicineKarolinska Institutet at Karolinska University Hospital HuddingeStockholmSweden
  2. 2.Growth and Development Research Center, Children’s Medical Center HospitalTehran University of Medical SciencesTehranIran
  3. 3.Immunology, Asthma and Allergy Research Institute, Children’s Medical Center HospitalTehran University of Medical SciencesTehranIran
  4. 4.Division of Rheumatology and Clinical Immunology, Medical SchoolUniversity Hospital FreiburgFreiburgGermany
  5. 5.Immunological Laboratory, Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran