Plasma CXCL4–DNA/RNA Complexes and Anti-CXCL4 Antibodies Modulation in an SSc Cohort under Iloprost Treatment.

Autor: Mennella, Anna, Stefanantoni, Katia, Palazzo, Raffaella, Ocone, Giuseppe, Pietraforte, Immacolata, Truglia, Simona, Bisconti, Ilaria, Pisacreta, Alba, Riccieri, Valeria, Lande, Roberto, Frasca, Loredana
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Zdroj: Reports (MDPI AG); Sep2024, Vol. 7 Issue 3, p66, 15p
Abstrakt: Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular and immunity alterations and skin/internal organ fibrosis. Aberrant levels of plasma CXCL4, CXCL4–RNA/DNA complexes, type I IFN (IFN-I) and anti-CXCL4 antibodies characterize SSc. These parameters influence each other: CXCL4–self-DNA/RNA complexes are triggers of IFN-I in plasmacytoid dendritic cells (pDCs), and anti-CXCL4 autoantibodies amplify this effect. Here, we assess the modulation over time of plasma CXCL4 and the related parameters of CXCL4–DNA/RNA complexes, anti-CXCL4 antibodies, IFN-α and TNF-α in an SSc cohort under the synthetic analogue of prostacyclin PGI2 (iloprost) treatment to address contribution of these parameters to pathogenesis and their role as biomarkers. Methods: We analyzed immunological parameters at baseline (T0) and after 3 (T3) and 6 (T6) months in 30 SSc patients. Responders were the patients that lowered their disease activity parameters after six months of treatment. Results: Anti-CXCL4 autoantibodies correlated with both IFN-α and TNF-α levels in SSc plasma. Responders significantly down-regulated serum IFN-α. In seven patients with a shorter disease duration, improvement coincides with a decrease in plasma IFN-α, CXCL4 and TNF-α. Iloprost efficiently blocks pDCs IFN-α production induced by CXCL4–DNA/RNA complexes in vitro. Conclusions: The data suggest a possible role of iloprost as a disease-modifying drug, mainly accompanied by down-regulation of plasma IFN-I levels. Since CXCL4, IFN-I and TNF-α down-modulation was evident and significant in improving SSc patients with a shorter disease duration, these results warrant future investigations on the early use of iloprost to slow SSc progression. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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