Jan Kurdybacha

Objectives: This study aimed to investigate the associations among cytokines of the IL-12 family in patients with systemic sclerosis (SSc) and to evaluate their relationships with the pro-inflammatory cytokines TNF-α and IL-6, the latent form of TGF-β1 (LAP-bound, without prior sample activation), clinical parameters, and disease subtypes. Methods: Concentrations of IL-12p70, IL-12p40, IL-23, IL-27, IL-35, IL-39, TNF-α, and IL-6 were measured in serum, whereas latent TGF-β1 concentrations were determined in plasma obtained from 60 patients with systemic sclerosis (SSc) and 21 age- and sex-matched healthy controls. Results: Compared with healthy controls, patients with SSc exhibited significantly elevated levels of IL-12p40, IL-23, and IL-35, whereas IL-27, TNF-α, and TGF-β concentrations were significantly reduced. Correlation analysis revealed significant negative associations between latent TGF-β1 and IL-6, IL-27, and IL-35. Significant positive correlations were observed between TNF-α and IL-6, TNF-α and IL-12p40, IL-35 and IL-12p40, IL-23 and IL-12p40, and IL-12p40 with both IL-6 and IL-12p70. No significant associations were identified between the investigated cytokines and the Medsger severity score, patient age, anti-centromere antibody (ACA) status, anti-topoisomerase I antibody (Scl-70) status, the presence of pulmonary fibrosis, or diffusing capacity of the lungs for carbon monoxide (DLCO). In contrast, IL-35 levels demonstrated significant moderate negative correlations with both the modified Rodnan Skin Score (mRSS) (ρ = −0.35, p < 0.01) and disease duration (ρ = −0.30, p < 0.05). Conclusions: These findings may indicate the presence of a complex network of associations among IL-12 family cytokines in systemic sclerosis.

Introduction: Biologic treatments have demonstrated increasing benefits for cardiovascular health in patients with rheumatoid arthritis (RA), including reductions in myocardial infarction risk factors, atherosclerosis progression, and the incidence of heart failure. This study aimed to compare treatment options: one combination of tumor necrosis factor inhibitors (adalimumab, etanercept) with methotrexate (MTX) and second treatment with anti-interleukin-6 (tocilizumab) – to determine whether cardiovascular effects are driven primarily by disease activity reduction or through distinct effects based on the mechanism of action. Moreover, we aimed to assess the influence of treatment on heart structure. Material and methods: This study included 120 RA patients on various therapies (etanercept, adalimumab, tocilizumab, and MTX) and compared them to 22 healthy controls. All participants underwent echocardiographic assessment to measure left ventricle (LV) mass, LV mass index, and LV hypertrophy type. Resting electrocardiograms were also conducted. Results: All patients showed normal LV function (ejection fraction > 50%). Patients treated with MTX exhibited larger right ventricular (28.1 mm vs. 21.1 mm, p < 0.05) and left atrial (37.5 mm vs. 31.1 mm, p < 0.01) dimensions compared to those on adalimumab. Additionally, MTX-treated patients had a higher LV mass index (106.8 vs. 90.9, p < 0.05) and the highest incidence of LV hypertrophy (56%), predominantly of the concentric type. Electrocardiographic findings showed a prolonged PR interval in patients on tocilizumab, while those on etanercept displayed a shortened PR interval. Disease activity was significantly lower in biologic-treated patients than in those receiving MTX. Conclusions: Biologics, irrespective of their specific mechanisms, significantly reduce disease acti­vity, which positively influences LV mass and reduces the incidence of LV hypertrophy. Additionally, biologics do not adversely affect cardiac electrical function.

Systemic sclerosis, a connective tissue disease of unknown etiology and unpredictable outcomes, is characterized by the fibrosis of the skin and internal organs, vasculopathy, and immune system dysregulation. The disease is classified into two main subtypes, which differ in clinical presentation, complications, and prognosis. While several biomarkers have been proposed to distinguish between these subtypes, none have achieved high sensitivity and specificity. The search for dependable markers that can differentiate between the two primary subtypes of systemic sclerosis continues. To address this gap, our study evaluated the utility of novel cardiac biomarkers, including growth differentiation factor 15 (GDF15), galectin-3, mid-regional pro-atrial natriuretic peptide (MR-proANP), glutathione S-transferase π, mid-regional adrenomedullin, and soluble urokinase plasminogen activator receptor (suPAR), in a cohort of 79 patients with both lcSSc and dSSc subtypes. The results demonstrated a significant elevation of GDF15 (medians: 2.07 vs. 1.10 ng/L; p < 0.001) and MR-proANP (92.55 vs. 65.60 pmol/L; p < 0.05) levels in SSc patients compared to healthy controls. Moreover, GDF15 (1.65 vs. 2.34 ng/mL; p < 0.05), MR-proANP (80.87 vs. 109.27 pmol/L; p < 0.05), and suPAR (1.83 vs. 2.44 ng/mL; p < 0.05) levels were notably higher in patients with dSSc compared to those with lcSSc. In the ROC analysis, only GDF-15, MR-proANP, and suPAR proved to have a statistically significant area under the curve (AUC). Patients with the GDF-15 ≥ 2182 ng/mL, MR-prANP ≥ 85.808 pmol/L, and suPAR ≥ 2.315 ng/mL have more than six-, eight-, and seven-times-higher odds for dcSSc, respectively. These findings highlight the potential of GDF15, suPAR, and MR-proANP as biomarkers for differentiating between the two main subtypes of systemic sclerosis.