Microparticle subpopulations are potential markers of disease progression and vascular dysfunction across a spectrum of connective tissue disease

Objective: Microparticles (MPs) are membrane-bound vesicles derived fromvascular and intravascular cells such as endothelial cells (EMPs) and platelets (PMPs). We investigated EMP and PMP numbers across a spectrum of autoimmune rheumatic diseases (AIRDs) with the aim of comparing the levels of, and relationship between, EMPs and PMPs. Methods: Patientswith Systemic Lupus Erythematosus (SLE) (n= 24), Systemic Sclerosis (SSc) (n= 24), Primary Raynauds Phenomenon (RP) (n= 17) and other CTD (n= 15) (Primary Sjogrens Syndrome, UCTD or MCTD) aswell as 15 healthy controlswere recruited. EMPs and PMPswere quantified using flowcytometry. Associations between MP levels and objective functional vascular assessments were evaluated. Results: SLE patients had significantly higher EMPs comparedwith healthy controls and SSc patients. Higher PMP levels were noted in SSc and primary RP when compared to healthy controls and 'other CTD' patients. A modest correlation was noted between EMP and PMP levels in healthy controls (Spearman r = 0.6, p = 0.017). This relationship appeared stronger in SLE (r = 0.72, p < 0.0001) and other CTD patients (r = 0.75, p < 0.0001). The association between EMPs and PMPs was notably less strong in SSc (r = 0.45, p = 0.014) and RP (r = 0.37, p = 0.15). A significantly lower EMP/PMP ratio was detected in SSc/RP patients in comparison to both healthy controls and SLE/other CTD patients. Higher EMPand PMP levelswere associated with higher digital perfusion following cold challenge in SSc. In contrast, higher PMP (but not EMP) levels were associated with lower digital perfusion at both baseline and following cold challenge in primary RP. Higher PMP levels were associated with greater endothelial-independent dilation in patients with SLE. Conclusion: MP populations differ across the spectrumof AIRDS, possibly reflecting differences in vascular cell injury and activation. MP levels are associated with functional assessments of vascular function and might have a role as novel vascular biomarkers in AIRDs. Significance and innovations: Levels of circulating endothelial and platelet microparticles differ between SSc/primary RP compared with SLE and other CTDs (UCTD, MCTD and Primary Sjogrens). MP release may occur within different vascular sites across these disease groups (macrovascular and microvascular). The association between circulatingMP levels and objective assessment ofmacro-andmicrovascular dysfunction within these disease areas suggests thatMPs might have a useful role as novel circulating biomarkers of vascular disease within the CTDs. (C) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license