Microparticles as autoantigens in systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of antibodies to components of the cell nucleus (antinuclear antibodies or ANAs) and the formation of immune complexes with nuclear antigens. These complexes can drive pathogenesis by depositing in the tissue to incite inflammation or induce cytokine production by cells of the innate immune system. While ANAs can bind to purified nuclear molecules, nuclear autoantigens in vivo most likely exist attached to other molecules or embedded in larger structures. Among these structures, microparticles (MPs) are membrane bound vesicles that are released from dead and dying cells by a blebbing process; MPs can also be released during activation of platelets. The presence of MPs in the blood or tissue culture media can be assayed by flow cytometry on the basis of light scattering as well as binding of marker antibodies to identify the cell of origin. As shown by biochemical analyses, MPs contain an ensemble of intracellular components including nuclear, cytoplasmic and membrane molecules. Because of the display of these molecules on the particle surface or in an otherwise accessible form, ANAs, including anti-DNA, can bind to particles. Levels of MPs are increased in the blood of patients with SLE, with flow cytometry demonstrating the presence of IgG-containing particles. In addition to forming immune complexes, MPs can directly stimulate immune responses. Together, these findings suggest an important role of particles in the pathogenesis of SLE and their utility as biomarkers.

Insights into the Procoagulant Profile of Patients with Systemic Lupus Erythematosus without Antiphospholipid Antibodies

“…The increase in TF-bearing MPs could come from damaged endothelial cells [ 40 ]. In support of this observation, we and other authors [ 35 , 39 ] have observed increased plasma levels of PAI-1, a marker of endothelial dysfunction, in patients with SLE. In addition, augmented PAI-1 accompanied higher MCF values.…”

“…The procoagulant profile in patients with SLE might also be due to the presence of MPs released by cells in response to activation or apoptosis. Given that SLE is characterized by chronic inflammation and tissue damage, it is not surprising that blood from patients with SLE contains more MPs [ 34 , 35 , 36 ], due to both activated and damaged cells. MPs support coagulation by the exposure of negatively charged phospholipids and TF.…”

“…These differences might rely on the inclusion criteria for patients with SLE or/and the use of distinct technical approaches for measuring MPs. Given that the MPs in SLE exhibit unique molecular and phenotypic features, including the infrequent expression of PS, their role in the pathogenesis of SLE and their utility as biomarkers have been suggested by many authors [ 35 , 39 ].…”

Electronic cigarettes containing nicotine increase endothelial and platelet derived extracellular vesicles in healthy volunteers

“…Extracellular vesicles (EVs), also known as microparticles or microvesicles are membrane bound vesicles that are released into the circulation upon cell activation and/or apoptosis [12]. EVs can expose and harbour bioactive molecules and seem actively involved in the homeostatic regulation [13,14].…”

Autoimmunity and SLE: Factual and Semantic Evidence-Based Critical Analyses of Definitions, Etiology, and Pathogenesis

“…Such studies are focused on distinct autoimmune processes that are unlinked from a solitary SLE context, as is indicated by the triangular 1 link of anti-dsDNA antibodies to SLE, infections and malignancies ( Figure 2A ). Autoimmunity to chromatin structures is, however, relevant for SLE ( 11 , 13 , 14 , 35 – 38 ), and for pathogenesis of organ manifestations like lupus nephritis, dermatitis and cerebral affections, as discussed below.…”