Background Patients with systemic autoimmune diseases display an increased risk of cardiovascular (CV) mortality. Inflammatory and immune-mediated mechanisms have been identified to promote atherosclerotic endothelial injury (1). Sjögren’s syndrome (SS) represents an interesting model to investigate pathogenetic mechanisms involved in atherosclerotic damage. Young SS patients are characterized by an accelerated subclinical atherosclerotic damage (2,3). However, exact pathogenic mechanisms involved in the precocious vascular damage in SS are still unclear. Recent evidence suggests that loss of endothelial integrity may involve defects in the vascular regenerative capacity provided by circulating endothelial progenitor cells (EPC) and generation of circulating microparticles (MPs). Endothelial (E) MPs represent an emerging marker of endothelial dysfunction in patients with CV diseases and increased numbers of EMPs have been demonstrated in diseases characterized by high inflammatory response, such as polymyalgia rheumatica (4). Increased levels of leukocyte and platelet MPs have been demonstrated in SS and have been identified as biomarkers of systemic cell activation. On the other hand, the role of EMPs in SS has been never investigated.
Objectives To evaluate endothelial injury degreein SS by quantification of circulating EMPs and their repair potential by EPCmeasurement and to analyze possible correlation with disease-specific clinical and immunologic features.
Methods 49 SS patients (48 female, 1 male) and 30 age- and sex-matched normal controls (NC) were enrolled. Number of circulating EMPs (CD31+/CD42-) and EPC (CD34+/CD133+/KDR+ and mature CD34+/KDR+) was quantified by FACS analysis. Parameters of disease activity and damage were measured by ESSDAI (inactive ≤ 2, active > 2) and SSDDI, respectively. Disease-related clinical features, laboratory markers of immunologic dysfunction and traditional CV risk factors were recorded.
Results SS patients displayed higher levels of EMPs and triple positive EPCs than NC (mean±SD: 565±223 vs 399±28 and 144±117 vs 74±54 n/mL, respectively, p<0.05) and lower count of mature EPCs than NC (234±188 vs 563±21 n/mL, p<0.05). The number of both triple positive and mature CD34+/KDR+ EPCs were inversely correlated with disease duration. Intriguingly, it was of interest the observation that, among patients, smokers displayed higher ESSDAI in comparison to non-smokers (p=0.004).
Conclusions This is the first evidence that SS may be associated with endothelium integrity loss toward generation of EMPs. Progenitors seem to be adequately released, particularly in early stages of the disease, so suggesting an attempt at revascularization. However, their ability to mature differs from healthy subjects and this may contribute to endothelial dysfunction. Of interest, among traditional CV risk factors, smoking may be associated with an higher risk of active disease. Further investigations, however, are needed to ascertain the role of EMPs and EPCs in promoting subclinical atherosclerotic damage in SS.
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Disclosure of Interest None Declared