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.