The Role of Microparticles in the Pathogenesis of Rheumatic Diseases

Christian Beyer; David S. Pisetsky

Abstract and Introduction

Abstract

Microparticles (MPs) are small membrane-bound vesicles that are emerging as important elements in the pathogenesis of rheumatic diseases owing to their pleiotropic effects on thrombosis, vascular reactivity, angiogenesis and inflammation. Released from cells during activation and apoptosis, MPs carry proteins, lipids and nucleic acids, and serve as platforms for enzymatic processes in thrombosis. Furthermore, MPs can transfer cytokines, receptors, RNA and DNA to modulate the properties of target cells. As MPs appear in the blood in increased numbers during rheumatic disease, they represent novel biomarkers that can be used to assess events in otherwise inaccessible tissues. Future research will define further the pathogenetic role of MPs and explore therapeutic strategies to block their release or signaling properties.

Introduction

Microparticles (MPs) are a heterogeneous group of membrane-bound vesicles that can act as unique signaling elements in the pathogenesis of rheumatic diseases. Once released from cells by membrane blebbing, MPs display diverse functional activities and can mediate intercellular communication. Importantly, in the context of rheumatic disease, MPs can regulate thrombosis, vascular reactivity, angiogenesis and inflammation. Consistent with a role of MPs in immunopathogenesis, patients with rheumatic disease show marked increases in the number of particles in the blood, which can reflect the extent and severity of the disease.^[1] This Review will, therefore, consider the origin and activity of MPs, their role as biomarkers, and the steps in disease where they can initiate or amplify underlying pathogenetic disturbances.

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Table 1. Microparticles as biomarkers of rheumatic diseases: clinical studies and findings
Study	Microparticle type and phenotype	Findings
*APS and SLE*
Combes et al.^[95] (1999)	PMPs: CD41; EMPs: CD51; LMPs: CD14	Increased numbers of EMPs in patients with lupus anticoagulant
Lazarus et al.^[34] (2000)	PMPs: CD41	Increased numbers of PMPs in patients with ITP or SLE plus thrombocytopenia
Joseph et al.^[47] (2001)	PMPs: CD41	Increased numbers of PMPs in SLE
Nagahama et al.^[48] (2001)	PMPs	Increased numbers of PMPs in SLE
Nagahama et al.^[44] (2003)	PMPs; LMPs: CD14	Increased numbers of PMPs and LMPs in APS
Dignat-George et al.^[42] (2003)	EMPs: CD51	Increased numbers of EMPs levels in APS or SLE patients with aPL
Pereira et al.^[45] (2006)	PMPs: CD61; EMPs: CD146; LMPs: CD45	Increased numbers of PMPs in SLE
Jy et al.^[43] (2007)	PMPs: CD31/CD42; EMPs: CD31/CD42	Increased numbers of EMPs in individuals with aPL Increased numbers of PMPs in APS
*SSc*
Guiducci et al.^[64] (2008)	PMPs: CD42; EMPs: CD144; LMPs: CD3, CD14, CD19, CD66b	Increased numbers of PMPs, EMPs and LMPs in SSc
Nomura et al.^[65] (2008)	PMPs; LMPs: CD14	Increased numbers of PMPs and LMPs in SSc
*Vasculitides*
Brogan et al.^[59] (2004)	PMPs: CD42a, CD62P; EMPs: CD62E, CD105, CD54, CD106	Increased numbers of EMPs and PMPs in children with systemic vasculitis
Daniel et al.^[60] (2005)	PMPs: CD41a; LMPs: CD66b	Increased numbers of PMPs and LMPs in acute vasculitis
Erdbruegger et al.^[61] (2008)	PMPs: CD42a, CD62P; EMPs: CD62E; LMPs: CD45, CD11b	Increased numbers of PMPs, EMPs and LMPs in acute vasculitis
*RA and other forms of arthritides*
Kniijff-Dutmer et al.^[49] (2002)	PMPs: Annexin V, CD61	Increased numbers of PMPs in RA
Berckmans et al.^[91] (2002)	PMPs: CD61; LMPs: CD4, CD8, CD14, CD20, CD66b, CD66e	Increased numbers of MPs in inflamed joints in RA and non-RA arthritides
Berckmans et al.^[90] (2004)	PMPs: CD61; LMPs: CD4, CD8, CD14, CD20, CD66e	Increased numbers of MP levels in inflamed joints in RA and non-RA arthritides
Biró et al.^[92] (2007)	MPs: Annexin V, C1q, C3, C4, CRP, IgG, IgM	Increased numbers of synovial MPs with C1q, C3, and C4 in RA
Messer et al.^[93] (2009)*	MPs: Annexin V	Increased numbers of synovial MPs in RA and crystalarthropathy
Umekita et al.^[96] (2009)	PMPs: CD61, CD42a; LMPs: CD66b, CD16	Increased numbers of PMPs but not LMPs in RA

*Use of ELISA instead of flow cytometry. Abbreviations: aPL, antiphospholipid antibodies; APS, antiphospholipid syndrome; CRP, C-reactive protein; EMPs, endothelium-derived microparticles; ITP, idiopathic thrombocytopenic purpura; LMPs, leukocyte-derived microparticles; MPs, microparticles; PMPs, platelet-derived microparticles; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SSc, systemic sclerosis.

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