Single nucleotide polymorphisms in non-HLA genes are involved in the development of rheumatoid arthritis (RA). SNPS in genes: PADI4 (rs2240340), STAT4 (rs7574865), CD40 (rs4810485), PTPN22 (rs2476601), and TRAF1 (rs3761847) have been described as risk factors for the development of autoimmune diseases, including RA. This study aimed to assess the prevalence of polymorphisms of these genes in the Polish population of patients with rheumatoid arthritis as compared to healthy controls. 324 subjects were included in the study: 153 healthy subjects and 181 patients from the Department of Rheumatology, Medical University of Lodz who fulfilled the criteria of rheumatoid arthritis diagnosis. Genotypes were determined by Taqman SNP Genotyping Assay. rs2476601 (G/A, OR = 2.16, CI = 1.27–3.66; A/A, OR = 10.35, CI = 1.27–84.21), rs2240340 (C/T, OR = 4.35, CI = 2.55–7.42; T/T, OR = 2.80, CI = 1.43–4.10) and rs7574865 (G/T, OR = 1.97, CI = 1.21–3.21; T/T, OR = 3.33, CI = 1.01–11.02) were associated with RA in the Polish population. Rs4810485 was also associated with RA, however after Bonferroni’s correction was statistically insignificant. We also found an association between minor alleles of rs2476601, rs2240340, and rs7574865 and RA (OR = 2.32, CI = 1.47–3.66; OR = 2.335, CI = 1.64–3.31; OR = 1.88, CI = 1.27–2.79, respectively). Multilocus analysis revealed an association between CGGGT and rare (below 0.02 frequency) haplotypes (OR = 12.28, CI = 2.65–56.91; OR = 3.23, CI = 1.63–6.39). In the Polish population, polymorphisms of the PADI4, PTPN22, and STAT4 genes have been detected, which are also known risk factors for RA in various other populations.

Numerous studies have shown that cf nDNA significantly rises in stress caused by exercise. However, during nuclear decondensation, released DNA is followed by histones. Histones are also a common disease marker. After PAD4 mediated hypercitrullination extracellular H3Cit exhibits high toxicity contributing to tissue damage which, in cases of systemic inflammation, may lead to multiorgan failure and finally to death. We tested whether circulating histones rise in response to strenuous exercise. Eleven average-trained men performed three treadmill exercise tests to exhaustion at speed corresponding to 70% VO2max separated by 72 h of resting. Blood was collected before and just after each bout of exercise and plasma proteins were measured using enzyme-linked immunosorbent assay, whereas platelet activity was estimated with Light Transmission Aggregometry. Both, circulating histones and PAD4 raised in response to exercise. Plasma citrullinated histones increased from 3.1 ng/mL to 5.96 ng/mL (p = 0.0059), from 3.65 ng/mL to 6.37 ng/mL (p = 0.02), and from 3.86 ng/mL to 4.75 ng/mL (p = 0.033) after the first, second, and third treadmill run, respectively. However despite the parallel increase, no significant correlation between citrullinated histone and aggregation or cell-free nDNA was found. Furthermore, positive correlations of cf nDNA with aggregation and PAD4, lactate with aggregation, and lactate with citrullinated histone have been observed.

Introduction: RA is a common autoimmune heterogeneous joint disease of still unknown etiology. One of the characteristic features of RA is oxidative stress, most probably induced and stimulated by inappropriate B and T-cell activity. We have hypothesized, that oxidative stress together with...

Introduction: Rheumatoid arthritis (RA) is a prevalent autoimmune disorder characterized by chronic joint inflammation and progressive bone erosion. Traditional autoantibodies, such as anti-citrullinated peptide antibodies (ACPAs) and rheumatoid factor (RF), are established markers associated with disease severity. Recent studies have identified anti-carbamylated protein (anti-CarP) antibodies as potential indicators of disease progression. Additionally, bone turnover markers and specific single nucleotide polymorphisms (SNPs) may influence RA pathogenesis. This study aimed to evaluate the correlation between autoantibody profiles, disease activity, bone turnover markers, and selected SNPs in a cohort of Polish RA patients.Material and methods: A total of 138 RA patients from the Department of Rheumatology, Medical University of Lodz, were enrolled. Disease activity was assessed using the Disease Activity Score in 28 joints by C-reactive protein (DAS28-CRP). Serum levels of RF, ACPAs, anti-CarP antibodies, and bone turnover markers (sclerostin, periostin, and Dickkopf-1) were measured using immunoassays. Genotyping for SNPs in PADI4 (rs2240340), STAT4 (rs7574865), and PTPN22 (rs2476601) genes was performed. Patients were categorized into two groups: those positive for anti-CarP antibodies, RF, and ACPA (triple-positive, n = 27) and those with other antibody combinations (n = 111).Results: Demographic characteristics, including age (mean approx. 61 years), gender distribution (approx. 75% female), treatment rates (approx. 75%), and glucocorticosteroid use (approx. 40%), were comparable between groups. The triple-positive group exhibited higher disease activity, with a greater number of painful joints (mean 10.07 vs. 7.72; p = 0.017), higher Visual Analogue Scale (VAS) scores for pain (mean 6.26 vs. 5.06; p = 0.018), elevated DAS28-CRP scores (mean 4.75 vs. 4.07; p = 0.037), and increased erythrocyte sedimentation rate (ESR) (mean 32.92 mm/h vs. 22.82 mm/h; p = 0.019). Serologically, the triple-positive group had significantly higher levels of anti-CarP (mean 29.19 ng/ml vs. 16.29 ng/ml; p < 0.0001) and ACPAs (mean 395.45 vs. 368.70; p < 0.0001), but lower RF levels (mean 164.01 vs. 453.40; p = 0.004). Bone turnover markers showed no significant differences between groups, though the difference in sclerostin levels approached statistical significance (p = 0.085), suggesting a possible association of higher bone formation inhibition with triple-positive status. No significant associations were found between the autoantibody profiles and the selected SNPs.Conclusions: The presence of anti-CarP antibodies, RF, and ACPA is associated with increased disease activity in RA patients. However, these autoantibody profiles do not significantly correlate with bone turnover markers or the selected genetic polymorphisms in this Polish cohort. Further research is warranted to elucidate the complex interactions between autoantibodies, bone metabolism, and genetic factors in RA.

Dermatomyositis with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies is a rare, poorly recognised and potentially life-threatening subtype of idiopathic inflammatory myo­pathies. Frequent amyopathic course, unique cutaneous lesions, symptoms interfering with other connective tissue diseases, and low awareness of the disease lead to a delay in establishing the proper diagnosis. Clinical presentations may differ among individuals, and three main patterns have been identified depending on the predominant symptoms and prognosis. Interstitial lung disease and vasculopathy contribute mostly to an unfavourable outcome. The study aimed to present different courses of anti-MDA5 myopathy and highlight the heterogenicity of the disease, based on real-life cases from one centre. This is also the first study to document renal involvement in the form of focal segmental glomerulosclerosis in patient with anti-MDA5 dermatomyositis. The review section broadly describes up-to-date knowledge on the subtypes of anti-MDA5 myopathy, thoroughly exploring its pathogenesis, clinical presentations and currently recommended standards of care.

Strenuous exercise increases circulating cell free DNA (cf DNA) and stimulates blood phagocytes to generate reactive oxygen species (ROS) which may induce DNA strand breaks. We tested whether: (A) elevated cf DNA in response to three repeated bouts of exhaustive exercise has decreased integrity; (B) each bout of exercise increases luminol enhanced whole blood chemiluminescence (LBCL) as a measure of ROS production by polymorphonuclear leukocytes. Eleven men performed three treadmill exercise tests to exhaustion separated by 72 hours of resting. Pre- and post-exercise concentrations and integrity of cf nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) and resting and fMLP-stimulated LBCL were determined. Each bout increased concentrations of cf n-DNA by more than 10-times which was accompanied by about 2-times elevated post-exercise rLBCL and fMLP-LBCL. Post-exercise cf n-DNA integrity (integrity index, I _206/78 ) decreased after the first (0.59±0.19 vs. 0.48±0.18) and second (0.53±0.14 vs. 0.44±0.17) bout of exercise. There were negative correlations between I _206/78 and rLBCL (ƍ=−0.37) and I _206/78 and fMLP-LBCL (ƍ=− 0.40) – analysis of pooled pre- and post-exercise data (n=66). cf-mt DNA integrity (I _218/97 ) did not alter in response to exercise. This suggests an involvement of phagocyte ROS in cf n-DNA strand breaks in response to exhaustive exercise.