T-cell specific upregulation of Sema4A as risk factor for autoimmunity in systemic lupus erythematosus and rheumatoid arthritis

The aim of the present study was to evaluate the impact of <i>SEMA4A</i> genetic variants on expression of sema4A protein and its relation to autoimmunity development in Systemic Lupus Erythematosus and Rheumatoid Arthritis patients. A total of 541 SLE patients, 390 RA patients and 607 healthy individuals were genotyped. We also assessed <i>SEMA4A</i> mRNA expression from whole blood cells and the in vitro protein production from resting and activated T lymphocytes as well as mature dendritic cells from healthy individuals stratified according to their genotypes for SLE/RA associated <i>SEMA4A</i> variants. Our results showed that T/T genotype for rs3738581 SNP is associated with both RA and SLE development (<i>p</i> = .000053, OR = 2.35; <i>p</i> = .0019, OR = 2.07, respectively; statistical power = 100%) and also to an increased in vitro sema4A production in active T lymphocytes. Our findings are indicative of a T cell-specific upregulation of sema4A in the presence of T/T genotype, being a risk factor for SLE and RA.