Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls. MPs were measured with flow cytometry and phenotyped according to phosphatidylserine expression (PS+/PS−), cellular origin and inflammatory markers. MPs, regardless of phenotype, are 2–10 times more abundant in SLE blood compared to controls. PS− MPs predominated in SLE, but not in controls (66% vs. 42%). Selectively in SLE, PS− MPs were more numerous in females and smokers. MP numbers decreased with declining renal function, but no clear association with disease activity was observed. The striking abundance of MPs, especially PS− MPs, suggests a generalized disturbance in SLE. MPs may be regarded as “liquid biopsies” to assess the production and clearance of dead, dying and activated cells, i.e. pivotal events for SLE pathogenesis.

Highlights

  • Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes

  • We further characterized these MPs in terms of their expression of markers that may indicate a role in inflammation or thrombosis

  • Nielsen et al reported that PS− MPs are more frequent in the blood of SLE patients compared to healthy controls, while PS+ MPs occurred at similar frequencies in SLE patients and controls[15]

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Summary

Introduction

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. Lupus primarily affects young women (90%) and, while its etiology is unknown, studies on patients and murine models suggest an important role in pathogenesis for disturbances in cell death as well as the clearance of dead and dying cells These disturbances may increase the amount of circulating cellular debris which is believed to contain self-antigens (e.g., nucleosomes and DNA) that can trigger B-cells to produce autoantibodies in susceptible individuals[4,5,6]. We further explored if the levels MPs are related to clinical and serological features of SLE

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