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The T cell regulator gene SH2D2A contributes to the genetic susceptibility of multiple sclerosis

Genes & Immunity volume 2, pages 263–268 (2001)Cite this article

Abstract

The T cell specific adapter protein (TSAd) encoded by the SH2D2A gene is involved in the control of T cell activation. The gene is located in the 1q21 region, which has been implicated in susceptibility to experimental allergic encephalomyelitis in the mouse. We therefore evaluated whether a polymorphic GA repeat (GA13–GA33) within the promoter region of the SH2D2A gene shows association to multiple sclerosis (MS). The frequency of the short alleles GA13–16 was increased among 313 Norwegian MS patients compared to 277 healthy controls (0.332 vs 0.249, OR 1.5, Pc = 0.03). Transmission disequilibrium analysis in 146 Scandinavian families with at least two affected sibs showed increased transmission of GA16 to MS patients. No linkage or association of MS to four genetic markers flanking the SH2D2A gene was observed. After activation of naive CD4+ T cells, T cells homozygous for MS associated short alleles displayed lower level of TSAd ex vivo than T cells carrying at least one long allele, which were not associated to MS. Since the SH2D2A protein modulates T cell activation, this may be a mechanism for how short SH2D2A alleles confer susceptibility to develop MS.

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Acknowledgements

We thank Dr Stephen Sawcer (University of Cambridge Neurology Unit, Addenbrooke’s Hospital, Cambridge, UK) for kind assistance with the linkage and transmission analysis. Tor Lea (Institute of Immunology, National Hospital, Oslo, Norway) provided the antibody for T cells as a generous gift, and he has also given valuable advice. Vibeke Sundvold (Institute of Immunology, National Hospital, Oslo, Norway) is acknowledged for technical advice on the transfection procedure. Jan Brinchmann (Institute of Immunology, National Hospital, Oslo, Norway) is acknowledged for advice on the procedure for isolation of CD4+ T cells and the FACS antibodies. Ingebjørg Knutsen (Institute of Immunology, National Hospital, Oslo, Norway) is acknowledged for her excellent technical assistance.

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Authors and Affiliations

  1. Institute of Immunology, The National Hospital, Oslo, N-0027, Norway

    K-Z Dai, HF Harbo, F Vartdal & A Spurkland

  2. Department of Neurology, Ullevål Hospital, Oslo, Norway

    EG Celius

  3. Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    A Oturai & PS Sørensen

  4. Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    LP Ryder, P Datta & A Svejgaard

  5. Department of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden

    J Hillert & S Fredrikson

  6. Department of Neurology, Lund University Hospital, Lund, Sweden

    M Sandberg-Wollheim

  7. Turku Immunology Centre and Department of Virology, University of Turku, Turku, Finland

    M Laaksonen

  8. Department of Neurology, Haukeland Hospital, Bergen, Norway

    K-M Myhr & H Nyland

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  1. K-Z Dai
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  2. HF Harbo
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Correspondence to A Spurkland.

Additional information

The project has received financial support from Statens Lånekasse, EU-Commission (Project no. BMH4-CT97–2422), the Health and Rehabilitation Research Fund, Norwegian Research Council (NFR project: 129081/310), Odd Fellow MS Society, Medinnova, and the MS Society of Ålesund.

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Dai, KZ., Harbo, H., Celius, E. et al. The T cell regulator gene SH2D2A contributes to the genetic susceptibility of multiple sclerosis . Genes Immun 2, 263–268 (2001). https://doi.org/10.1038/sj.gene.6363774

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