Loss of function of a lupus-associated FcγRIIb polymorphism through exclusion from lipid rafts
Nature medicine, 2005•nature.com
Dysfunction of receptors for IgG (FcγRs) has been thought to be involved in the
pathogenesis of systemic lupus erythematosus (SLE). We show that a recently described
SLE-associated polymorphism of FcγRIIb (FcγRIIbT232), encoding a single transmembrane
amino acid substitution, is functionally impaired. FcγRIIbT232 is unable to inhibit activatory
receptors because it is excluded from sphingolipid rafts, resulting in the unopposed
proinflammatory signaling thought to promote SLE.
pathogenesis of systemic lupus erythematosus (SLE). We show that a recently described
SLE-associated polymorphism of FcγRIIb (FcγRIIbT232), encoding a single transmembrane
amino acid substitution, is functionally impaired. FcγRIIbT232 is unable to inhibit activatory
receptors because it is excluded from sphingolipid rafts, resulting in the unopposed
proinflammatory signaling thought to promote SLE.
Abstract
Dysfunction of receptors for IgG (FcγRs) has been thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We show that a recently described SLE-associated polymorphism of FcγRIIb (FcγRIIbT232), encoding a single transmembrane amino acid substitution, is functionally impaired. FcγRIIbT232 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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