Interferons (<i>IFN-A/-B/-G</i>) Genetic Variants in Patients with Mixed Connective Tissue Disease (MCTD)

• Main Authors: Agnieszka Paradowska-Gorycka, Anna Wajda, Barbara Stypinska, Ewa Walczuk, Marcela Walczyk, Anna Felis-Giemza, Aleksandra Poluch, Marzena Olesińska
• Format: Article
• Language: English
• Published: MDPI AG 2019-11-01
• Series: Journal of Clinical Medicine
• Subjects: mctd; genetics; ifn; pathogenesis
• Online Access: https://www.mdpi.com/2077-0383/8/12/2046

Mixed connective tissue disease (MCTD) is a rare complex autoimmune disease in which autoantigens are recognized by endosomal TLRs. Their activation induces a higher secretion of the type I interferons, IFN-&#947; and the up-regulation of the INF-inducible genes. The present study aimed to investigate whether SNPs that are located in the IFN-A, IFN-B, and IFN-G genes are associated with MCTD. 145 MCTD patients and 281 healthy subjects were examined for IFN-A, IFN-B, and IFN-G genetic variants by TaqMan SNP genotyping assay. ELISA determined IFN-&#945;/-&#946;/-&#947; serum levels. Among the seven tested SNPs, four polymorphisms: IFN-A rs10757212, IFN-A rs3758236, IFN-G rs2069705, IFN-G rs2069718, as well as INF-G rs1861493A/rs2069705A/rs2069718G haplotype were significantly associated with a predisposition for MCTD. Raynaud&#8217;s phenomenon, erosive arthritis, swollen hands and fingers, and sclerodactyly were significantly more frequently observed in MCTD patients with IFN-G rs2069718 G allele than in patients with IFN-G rs2069718 A allele. We also found that anti-U1-A autoantibodies most frequently occurred in MCTD patients with rs2069718 GA genotype, while the IFN-G rs2069705 AG and rs2069718 GA genotypes might be a marker of anti-Ro60 presence in MCTD patients. Our results indicate that IFN-G genetic variants may be potential genetic biomarkers for MCTD susceptibility and severity.