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An evolutionary approach to the medical implications of the tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) gene

Genes & Immunity volume 10, pages 566–578 (2009)Cite this article

Abstract

Coding variants in tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) have been implicated in common variable immunodeficiency (CVID), but the functional effects of such mutations in relation to the development of the disease have not been entirely established. To examine the potential contribution of TNFRSF13B variants to CVID, we have applied an evolutionary approach by sequencing its coding region in 451 individuals belonging to 26 worldwide populations, in addition to controls, patients with CVID and selective IgA deficiency (IgAD) from Italy. The low level of geographical structure for the observed genetic diversity and the several neutrality tests performed confirm the absence of recent population-specific selective pressures, suggesting that TNFRSF13B may be involved also in innate immune functions, rather than in adaptive immunity only. A slight excess of rare derived alleles was found in patients with CVID, and thus some of these variants may contribute to the disease, implying that CVID probably fits the rare variants rather than the common disease/common variant paradigm. This also confirms the previous suggestion that TNFRSF13B defects alone do not cause CVID and that such an extremely heterogeneous immunodeficiency might be more likely related to additional, still unknown environmental and genetic factors.

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Acknowledgements

This work was supported by Grants RFO ex 60% University of Bologna to DL, GSP02476 to SF, seventh framework programmes of the European Union Grant HEALTH-F2-2008-201549 to IQ and by Spanish Ministry of Science Grant BFU-63657 to FC.

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Author notes

  1. M Sazzini and R Zuntini: These authors contributed equally to this work.

Authors and Affiliations

  1. Dipartimento di Biologia Evoluzionistica Sperimentale, Area Antropologia, Università di Bologna, Bologna, Italy

    M Sazzini & D Luiselli

  2. Laboratorio di Genetica Medica, Azienda Ospedaliero-Universitaria Policlinico S.Orsola Malpighi, Bologna, Italy

    R Zuntini, G Romeo & S Ferrari

  3. Department of Immunology, Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    S Farjadian

  4. Dipartimento di Immunologia Clinica, Università di Roma ‘La Sapienza’, Roma, Italy

    I Quinti

  5. Dipartimento Pediatrico, Università di Bologna, Bologna, Italy

    G Ricci

  6. Departament de Ciències Experimentals i de la Salut, Institute of Evolutionary Biology (UPF-CSIC), Universitat Pompeu Fabra, Barcelona, Spain

    F Calafell

  7. CIBER Edipemiología y Salud Pública, Barcelona, Spain

    F Calafell

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  1. M Sazzini
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Correspondence to F Calafell.

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Sazzini, M., Zuntini, R., Farjadian, S. et al. An evolutionary approach to the medical implications of the tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) gene. Genes Immun 10, 566–578 (2009). https://doi.org/10.1038/gene.2009.43

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