Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts.

Floto, R Andres; Clatworthy, Menna R; Heilbronn, Karen R; Rosner, Dalya R; MacAry, Paul A; Rankin, Angela; Lehner, Paul J; Ouwehand, Willem H et al. · Nat Med · 2005

basic_science · Level V

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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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