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Association of the co-stimulator OX40L with systemic lupus erythematosus

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Abstract

The archetypal systemic autoimmune disease systemic lupus erythematosus (SLE) has incompletely understood pathogenesis, although evidence suggests a strong genetic component. Unlike organ-specific autoimmune diseases such as type 1 diabetes, the genetics of lupus are not as dominated by the effect of a single locus. Undoubtedly, the major histocompatibility complex is the greatest and most consistent genetic risk factor in SLE susceptibility; however, recent candidate gene and whole genome association (WGA) studies have identified several other genes that are likely to advance our understanding of this complex disease. One of these, the TNF superfamily member OX40L, interacts with its unique receptor OX40, to maintain T cell memory by providing a late-stage co-stimulatory signal to sustain the survival of activated T cells. The precise immunological consequences are yet to be determined; however, signalling through OX40-OX40L is bidirectional and the reverse signalling pathway via OX40L may quantitatively enhance B cell proliferation to augment the B cell hyperactivity found in SLE. Like OX40L, several genes recently identified in WGA studies are components of B cell pathways. Collectively, these genes will help us to unravel the mechanisms by which aberrant B cell signalling results in lupus pathogenesis.

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Authors and Affiliations

  1. Molecular Genetics and Rheumatology, Imperial College London, London, UK

    Harinder Manku, Deborah S. Cunninghame Graham & Timothy J. Vyse

  2. Rheumatology Section, Division of Medicine, Hammersmith Campus, Imperial College, London, W12 0N, UK

    Timothy J. Vyse

Authors
  1. Harinder Manku
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  2. Deborah S. Cunninghame Graham
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  3. Timothy J. Vyse
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Correspondence to Timothy J. Vyse.

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Manku, H., Graham, D.S.C. & Vyse, T.J. Association of the co-stimulator OX40L with systemic lupus erythematosus. J Mol Med 87, 229–234 (2009). https://doi.org/10.1007/s00109-008-0431-2

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  • DOI: https://doi.org/10.1007/s00109-008-0431-2

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