title: Microparticle subpopulations are potential markers of disease progression and vascular dysfunction across a spectrum of connective tissue disease.
abstract: OBJECTIVE
  Microparticles (MPs) are membrane-bound vesicles derived from vascular 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
  Patients with 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) as well as 15 healthy controls were recruited. EMPs and PMPs were quantified using flow cytometry. Associations between MP levels and objective functional vascular assessments were evaluated.
  
  
  RESULTS
  SLE patients had significantly higher EMPs compared with 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 (Spearmanr= 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 EMP and PMP levels were 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.
  
  
  CONCLUSIONS
  MP populations differ across the spectrum of 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.
  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 circulating MP levels and objective assessment of macro- and microvascular dysfunction within these disease areas suggests that MPs might have a useful role as novel circulating biomarkers of vascular disease within the CTDs.
authors.affiliation: Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, United Kingdom; NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospital NHS Foundation Trust and Manchester Academic Health Science Centre, Manchester, United Kingdom; Healthcare Science Research Institute, Manchester Metropolitan University, Manchester, United Kingdom.
authors.forename: E M
authors.initials: EM
authors.lastname: McCarthy
authors.affiliation: Healthcare Science Research Institute, Manchester Metropolitan University, Manchester, United Kingdom.
authors.forename: D
authors.initials: D
authors.lastname: Moreno-Martinez
authors.affiliation: Healthcare Science Research Institute, Manchester Metropolitan University, Manchester, United Kingdom.
authors.forename: F L
authors.initials: FL
authors.lastname: Wilkinson
authors.affiliation: Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom; Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
authors.forename: N J
authors.initials: NJ
authors.lastname: McHugh
authors.affiliation: Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, United Kingdom; NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospital NHS Foundation Trust and Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: I N
authors.initials: IN
authors.lastname: Bruce
authors.affiliation: Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom; Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
authors.forename: J D
authors.initials: JD
authors.lastname: Pauling
authors.affiliation: Healthcare Science Research Institute, Manchester Metropolitan University, Manchester, United Kingdom.
authors.forename: M Y
authors.initials: MY
authors.lastname: Alexander
authors.affiliation: Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, United Kingdom; NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospital NHS Foundation Trust and Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: B
authors.initials: B
authors.lastname: Parker
keywords: Endothelial microparticles; Platelets; Systemic lupus erythematosus; Systemic sclerosis