Association of the interferon-gamma receptor variant (Val14Met) with systemic lupus erythematosus

Genetic factors seem to play a significant Introduction role in susceptibil ity to systemic lupus erythematosus (SLE). The purpose of this study was to investigate whether the amino acid polymorphism (Val14Met) found within th e IFN-gamma receptor gene (IFNGR1) plays a prominent role in susceptibility to SLE. We found Val14Met located at the COOH terminal of the signal pepti de of the IFN-gamma receptor. There was a significant difference in this po lymorphism frequency between SLE patients and healthy populations. To clari fy whether this amino acid substitution resulted in the alteration of the r eceptor function, we evaluated the induction of HLA-DR antigen expression o n B cells by IFN-gamma stimulation. There was also a significant difference in the induction of HLA-DR by IFN-gamma stimulation between B cells. Furth ermore, an intracellular cytokine assay indicated that the Th1/Th2 balance of Th cells bearing the variant receptor shifted to Th2. The genetic polymo rphism found within the IFN-gamma receptor gene (Val14Met) may result in a shift to Th2, and this shift may increase susceptibility to SLE.