Background In systemic sclerosis (SSc), systemic remodeling, microvascular injuries and production of autoantibodies are well known as disease hallmarks. However, the master regulator of these characteristics is still unclear. Microparticle (MP) is a small membrane vesicle, released from various kinds of cells, and distributes systemically through circulation1). Recent reports revealed that MP contains various growth factors, proteases and cytokines including TGF-b2), suggesting that MP can contribute to immune and mesenchymal responses as a conveyor3). and involve with disease process of SSc. Although, the possible involvement of MPs in the pathogenesis of SSc is indicated, the detailed association of MPs including MP subsets with SSc is not well clarified.
Objectives To elucidate the association between circulating MP subsets and patients' characteristic of SSc.
Methods Thirty-six patients with SSc and 13 healthy controls were involved in this study. Platelet-rich plasma containing microparticles was isolated from whole blood using gradient centrifugation and analyzed using flow cytometer. MP was defined as particles smaller than 1.0 μm diameter using Megamix®, and identified each MP subsets based on expression of cell type-specific surface markers; platelet (CD31+CD41+), endothelial cell (CD31+CD41-) and monocyte (CD14+CD45+) using fluorescence-tagged antibodies. Clinical information was retrospectively collected from patients' records, and the correlation with the number of each MP subset was analyzed.
Results Mean age of 36 patients with SSc was 60.9±1.8 years, 94% was female, and mean disease duration was 11.2±9.5 years. Patients with diffuse cutaneous SSc (dcSSc) was 6 (17%). As for the proportion of MP subsets, platelet-derived MP (PMP) was the largest subset, followed by endothelial cell-derived MP (EMP) and monocyte-derived MP (MoMP) in all samples. In patients with SSc, the number of total MP and all MP subsets were higher than those in healthy controls (p<0.05). Also, all MP subsets were significantly higher in patients with dcSSc compared to limited cutaneous SSc (p<0.001). We also found that the number of PMP, EMP and MoMP were higher in patients who were positive against anti-topoisomerase I antibody than those negative (p<0.01, p<0.05 and p<0.05, respectively), whereas there were no significant differences in the numbers of each MP subset between the patients positive or negative against other SSc-specific autoantibodies. In addition, the number of PMP and EMP were higher in patients with interstitial lung disease than those without (p<0.05). Moreover, all MP subsets were significantly inversely correlated with the percentage of predicted forced vital capacity (p<0.05, p<0.01, and p<0.01, respectively).
Conclusions These results suggest that MP subsets are associated with extended fibrotic phenotype in patients with SSc, and might be utilized as novel biomarkers.
Bayer C et al. Nat Rev Rheumatol. 6:21–9, 2010.
Antonyak MA et al. Method Mol Biol. 1165:147–73, 2014.
Budoni M et al. Cell Transplant. 22:369–79, 2013.
Disclosure of Interest None declared