CXCL4 in undifferentiated connective tissue disease at risk for systemic sclerosis (SSc) (previously referred to as very early SSc)

Abstract

The aim of the study was to evaluate CXCL4 levels in undifferentiated connective tissue disease at risk for SSc (UCTD-SSc-risk) and confirm its increase and investigate its prognostic value. Serum CXCL4 levels were measured in 45 patients and 24 controls. CXCL4 was significantly higher in UCTD-SSc-risk patients than in controls. It resulted higher in patients with a shorter disease duration and in those lacking capillaroscopic alterations. We confirm that CXCL4 levels are increased in UCTD-risk-SSc patients. Further studies are needed to investigate the role of CXCL4 assessment in UCTD-risk-SSc.

New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis

“…Interestingly, anti-CXCL4 autoantibodies are significantly higher in patients with pitting scars in the lsSSc, but significantly lower in those with eaSSc. Since CXCL4 is highly up-regulated in eaSSc (especially in the diffuse form [7]), as well as in VEDOSS [30], one could speculate that the initial production of autoantibodies to CXCL4 could serve to neutralize CXCL4 excess, which may also block excess of IFN-I production at the beginning of the SSc symptoms. In this regard, we have shown that the levels of CXCL4-DNA complexes in eaSSc greatly correlates with amounts of IFN-I in blood [12].…”

CXCL4 drives fibrosis by promoting several key cellular and molecular processes

“…Previously, serum derived from individuals with SSc has been shown to induce EndMT in dermal microvascular endothelial cells (Manetti et al, 2017). Because of the high amount of CXCL4 in the circulation of these individuals (van Bon et al, 2014b;Haddon et al, 2017;Valentini et al, 2017;Volkmann et al, 2016), it is likely that CXCL4 might be a driving force in Using a genetic approach (knockout and overexpression) and a blocking antibody, we show the essential role of CXCL4 in fibrosis development in the skin, lungs, and heart using two independent fibrosis models and the therapeutic potential of targeting CXCL4 against fibrosis. Our study also demonstrates that CXCL4 directly induces myofibroblast differentiation from different precursor cells, including stromal cells and endothelial cells.…”

Platelet Dysfunction and Its Role in the Pathogenesis of Psoriasis

“…Platelet factor 4 (PF4) and β-thromboglobulin (β-TG) are the most abundantly expressed CXC chemokines in platelet α-granules that could be released in high concentrations following activated platelets [48]. Significant differences in plasma levels of PF4 or β-TG were found between many inflammatory skin diseases and normal controls, such as systemic sclerosis [49], allergic contact dermatitis [50], and atopic dermatitis [51], elevated expression indicating the critical role of platelet activation. β-TG together with PF4 levels in psoriasis was also reported to be higher than in healthy controls, and PF4 levels were correlated with PASI [51].…”