Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts |
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| Authors: | Floto R Andres Clatworthy Menna R Heilbronn Karen R Rosner Dalya R MacAry Paul A Rankin Angela Lehner Paul J Ouwehand Willem H Allen Janet M Watkins Nicholas A Smith Kenneth G C |
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| Affiliation: | Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge, Cambridge CB2 2XY, UK. arf27@cam.ac.uk |
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| Abstract: | Dysfunction of receptors for IgG (FcgammaRs) has been thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We show that a recently described SLE-associated polymorphism of FcgammaRIIb (FcgammaRIIbT(232)), encoding a single transmembrane amino acid substitution, is functionally impaired. FcgammaRIIbT(232) is unable to inhibit activatory receptors because it is excluded from sphingolipid rafts, resulting in the unopposed proinflammatory signaling thought to promote SLE. |
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