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Sequence Analysis of TNFRSF13b, Encoding TACI, in Patients with Systemic Lupus Erythematosus

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B cell activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL), and their receptors BAFF receptor (BAFFR), B cell maturation antigen (BCMA), and transmembrane activator and CAML interactor (TACI) are involved in the regulation of B cell homeostasis and differentiation. BAFF overexpression leads to systemic lupus erythematosus (SLE) in mice and elevated BAFF levels have been observed in human SLE and mouse models for SLE. Furthermore, genetic inactivation of TACI in mice results in a SLE-like phenotype. Based on our recent finding that TACI is mutated in patients with common variable immunodeficiency, of whom more than 30% suffer from autoimmune conditions, we analyzed TACI in humans with SLE. Sequence analysis of TNFRSF13b/TACI in 119 unrelated SLE patients revealed four variants: R20C in exon 1, R72H in exon 3, the silent variation c.327 G > A in exon 3, and A181E in exon 4. No significant association with any of these variants was found, when compared to the frequencies of the variants in a healthy control cohort. Furthermore, the mutated alleles R20C and R72H did not segregate with the SLE phenotype in familial cases of SLE. Thus, our evaluation of the coding region of TNFRSF13b/TACI did not reveal any deleterious or disease-associated mutations.

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ACKNOWLEDGMENTS

We are indebted to Dr. Pascal Schneider for providing us with the Flag-ACRP-hAPRIL construct. Grant support: Deutsche Forschungsgemeinschaft SFB620/C2; EU SP23-CT-2005-006411; NIH/NIAID: USIDnet grant # NO1-A1-30070 (B. G.), BMBF KN Rheuma C2.12 (T.W. and R.E.S) and the German Federal Ministry of Education and Research, Competence Network Rheumatism 01 GI 9949/C2.13 (I. M.). C.B. and S.B. are supported by the Primary Immunodeficiency Association (PIA) and the Medical Research Council (MRC), UK.

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Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Hugstetterstr. 55, 79106, Freiburg, Germany

    Ulrich Salzer

  2. Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

    Chiara Bacchelli, Sylvie Buckridge, H. Bobby Gaspar & Adrian J. Thrasher

  3. Department of Clinical Immunology, Medical School Hannover, D-30625, Hannover, Germany

    Torsten Witte & Reinhold E. Schmidt

  4. Clinical Research Unit for Rheumatology, University Medical Center Freiburg, Breisacher Str. 66 (ZKF), 79106, Freiburg, Germany

    Ulrike Buchegger-Podbielski, Rita Rzepka & Inga Melchers

  5. Department of Immunology and Molecular Pathology, Royal Free Hospital, University College London, London, NW3-2QG, UK

    Jennifer Birmelin & Bodo Grimbacher

  6. Department of Immunology and Molecular Pathology, Royal Free Hospital, University College London, Pond Street, London, NW3-2QG, UK

    Bodo Grimbacher

Authors
  1. Ulrich Salzer
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  2. Jennifer Birmelin
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  3. Chiara Bacchelli
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  4. Torsten Witte
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  5. Ulrike Buchegger-Podbielski
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  6. Sylvie Buckridge
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  7. Rita Rzepka
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  8. H. Bobby Gaspar
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  9. Adrian J. Thrasher
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  10. Reinhold E. Schmidt
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  11. Inga Melchers
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  12. Bodo Grimbacher
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Corresponding author

Correspondence to Bodo Grimbacher.

Additional information

Inga Melchers and Bodo Grimbacher contributed equally to this work.

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Salzer, U., Birmelin, J., Bacchelli, C. et al. Sequence Analysis of TNFRSF13b, Encoding TACI, in Patients with Systemic Lupus Erythematosus. J Clin Immunol 27, 372–377 (2007). https://doi.org/10.1007/s10875-007-9094-y

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  • DOI: https://doi.org/10.1007/s10875-007-9094-y

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