Increased frequency of the PTPN22W* variant in primary Sjogren's Syndrome: Association with low type I IFN scores

•PTPN22W* risk variant confers increased susceptibility for primary Sjogren's Syndrome development.•PTPN22W* carriage associates with low type I IFN scores in peripheral blood.•Our results support the concept of distinct genetic background and associated immune pathways among pSS subsets.

Recent data suggest the association of the autoimmune gene variant PTPN22W* with dampened type I Interferon (IFN) responses, seen in a subset of primary Sjogren's Syndrome (pSS) patients. We sought to explore the potential contribution of PTPN22W* in this setting. PTPN22W* was identified in DNA samples derived from 352 pSS patients and 482 healthy controls (HC). Type I IFN score was determined in available peripheral blood cDNA of 164 pSS patients by Real-Time PCR. Increased prevalence of the PTPN22W* variant was detected in pSS patients compared to HC [9.7% vs 5.0%, p-value: 0.02]. Of interest, only the low but not the high type I IFN pSS subgroup displayed higher PTPN22W* rates compared to HC (12.2% vs 5.0%, p-value: 0.03). PTPN22W* risk variant increases susceptibility for pSS, particularly the low type I IFN subset implying the presence of distinct genetic backgrounds among low and high type I IFN autoimmune subgroups.