Variations in the interferon and TLR3 genes may be associated with susceptibility to systemic lupus erythematosus and its clinical presentation.

The study aimed to explore the pontential impact of 10 polymorphisms within IFN-α, IFN-ß1, IFN-γ and TLR3 genes on SLE phenotype and susceptibility and to study the relationship between specific genotypes and clinics. Whole blood samples from SLE patients and healthy controls was obtained. DNA was extracted from the peripheral blood by the QIAamp DNA Blood Mini Kit (Qiagen). The quality and quantity of isolated DNA was estimated by the Quawell Q5000 spectrophotometer. We genotyped SLE patients and healthy subjects using real-time PCR (QuantStudio 5 thermocycler). The study suggests that IFN-γ rs2069705, IFN-γ rs2069718 and IFN-α rs3758236 polymorphisms have a protective role in SLE. We observed relations between TLR3 rs3775292, IFN-ß1 rs7873167, IFN-γ rs2069705, TLR3 rs3775291 and TLR3 rs5743305 polymorphisms and clinical picture of SLE patients. We found associations between the IFN-α rs3758236, IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493 and IFN-ß1 rs10964831 polymorphisms and the clinical manifestation of the SLE and/or its comorbidities. We perceived links between IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493, TLR3 rs3775291, TLR3 rs3775292 and TLR3 rs5743305 polymorphisms and the occurrence of autoantibodies. Our study presented the relationship between IFN and TLR gene polymorphisms with SLE susceptibility, phenotype and autoantibodies profile. This study propose that polymorphisms within interferons and TLR3 genes can be engaged in the SLE pathogenesis and course.

Variety of endosomal TLRs and Interferons (IFN-α, IFN-ß, IFN-γ) expression profiles in patients with SLE, SSc and MCTD.

We investigated Toll-like receptor (TLR)-3/-7/-8/-9 and interferon (IFN)-α/ß/γ mRNA expression in whole blood and serum IFN-α/ß/γ levels in patients with mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) and in healthy subjects to assess the association between the TLR-IFN expression and severity of and susceptibility to diseases, and identify potential biomarkers. Expression of the IFN-γ, TLR-3 and TLR-8 was detected only in SLE patients. TLR-7, IFN-α and IFN-ß expression was highest in SLE, while TLR-9 expression was highest in SSc patients. In SLE and MCTD patients a strong correlation was observed between TLR-7 and IFN-α expression and IFN-ß and IFN-α expression. In MCTD patients, negative correlation between IFN-α and TLR-9 and TLR-7 and TLR-9 was revealed. TLR-9 expression in anti-U1-70k-negative, anti-C negative and anti-SmB-negative MCTD patients was higher than in MCTD-positive patients. We observed negative correlations between serum IFN-α levels and TLR-7 expression and C3 and C4 levels in SLE patients. In SLE patients we observed that with increased IFN-γ, TLR-3 and TLR-8 expression increased the value of C3 and C4. Our results confirmed that the endosomal TLR-IFN pathway seems to be more important in SLE than in MCTD or SSc, and that IFN-α and IFN-ß may be possible biomarkers for SLE.

Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients.

Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD.

Association of single nucleotide polymorphisms in the IL27 gene with rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. Interleukin 27 (IL-27) is a novel pro-/anti-inflammatory cytokine, an excellent candidate for chronic inflammatory disease studies. The aim of the study was to identify polymorphisms in the IL-27 gene and their possible association with susceptibility to and severity of RA. Two hundred and seventy-four patients with RA and of 295 healthy individuals were examined for -924A/G and 4730T/C IL27 gene polymorphisms using PCR-RFLP method and TaqMan SNP genotyping assay, respectively. Haplotype frequencies of IL-27 polymorphisms were estimated using SHEsis platform. Frequencies of the -924GG genotype and the -924G allele were statistically higher in RA patients comparing with the healthy control group (P = 0.008 and P = 0.004, respectively). Overall, strong LD was observed between the IL27 gene -924A/G and 4730 T/C polymorphisms (D' = 0.613, r2 = 0.199). From four possible haplotypes, frequencies of two (CA and CG) showed significant differences between both examined groups (respectively: P < 0.001 and P = 0.001062). The genotype-phenotype analysis showed significant association between the IL-27 4730 T/C polymorphism and HAQ score and means value of the ESR, additionally they revealed that individuals with the polymorphic allele -924G had more advanced disease than wild-type allele carriers. Present findings indicated that IL27 -924A/G polymorphism may be involved in susceptibility to RA in the Polish population.