The authors declare that they have no competing interest.
LVI established the clinical database and the corresponding biobank, developed and performed flow cytometry of microparticles, was responsible for data acquisition, handling, and statistical analysis, and wrote the manuscript. SU helped establishing the clinical database and the acquisition of clinical data. OOE provided significant assistance in flow cytometry method development and participated in study design and coordination. CTN participated in sample collection and in study design and coordination. PH helped establishing the clinical database and helped to draft the manuscript. TK contributed to study design and coordination. NH conceived the study, participated in its design and coordination, participated in data interpretation and helped to draft, comment and revise the manuscript. SJ conceived the study, and participated in its design and coordination, performed statistical analysis, data interpretation and helped to draft, comment, and revise the manuscript. All authors read and approved the final manuscript.
Endothelial damage and activation may play central roles in the pathogenesis of systemic sclerosis (SSc) and are reflected by microparticles (MPs) and soluble selectins. The objective of this study was to determine if these potential biomarkers are associated with specific organ involvements or cutaneous subgroups of SSc patients.
MPs in platelet-poor plasma from 121 patients with SSc, 79 and 42 with limited and diffuse cutaneous disease, respectively, were characterized by flow cytometry for their capacity to bind annexin V in combination with surface markers of either platelets (PMPs), leukocytes (LMPs) or endothelial cells (EMPs). Soluble E- and P-selectin levels were determined in plasma. By correlation analyses, this was held against involvement of skin, lung function, lung fibrosis, pulmonary artery hypertension, and serology.
None of the markers were associated with cutaneous subgroups of SSc. Concentrations of annexin V non-binding EMPs and annexin V non-binding LMPs were negatively correlated to pulmonary diffusing capacity (DLCO) (r = -0.28; p = 0.003; r = -0.26; p = 0.005) and forced vital capacity (FVC) (r = -0.24; p = 0.009; r = -0.29; p = 0.002), driven by patients with limited and diffuse cutaneous disease, respectively. Soluble E-selectin levels correlated negatively to DLCO (r = -0.21, p = 0.03) and FVC (r = -0.25; p = 0.007); and soluble P-selectin correlated negatively to DLCO (r = -0.23, p = 0.01).
Negative correlations between annexin V non-binding EMP and LMP concentrations with lung function parameters (DLCO and FVC) differed between limited and diffuse cutaneous subsets of SSc, indicative of various pathogeneses of lung involvement in SSc, possibly with a differential role of MPs.
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- Cross-sectional study of soluble selectins, fractions of circulating microparticles and their relationship to lung and skin involvement in systemic sclerosis
Line V. Iversen
Christoffer T. Nielsen
Niels H.H. Heegaard
- BioMed Central
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