AUTOIMMUNITY

Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging.

Abstract

Purpose of review

Systemic lupus erythematosus (SLE) is characterized by autoantibodies directed against nuclear autoantigens normally concealed from immune recognition in healthy individuals. Here, we summarize recently identified mechanisms of abnormal cell death leading to exposure and aberrant processing of nucleoprotein self antigens, and discuss their role in the SLE pathogenesis.

Recent findings.

During the past few years, the unveiling of several new forms of cell death has expanded our understanding beyond the simple view of ‘apoptotic’ versus ‘necrotic’ cell death. SLE patients show abnormalities in cell death at several levels, including increased rates of apoptosis, necrosis, and autophagy, as well as reduced clearance of dying cells. These abnormalities lead to an increased autoantigen burden and antigen modifications, such as nucleic acid oxidation that increases the inflammatory properties of self antigens. Recent investigations have highlighted the role of opsonins in determining the immunogenic versus tolerogenic characteristics of self antigens.

Summary

Dysregulation of different forms of programmed cell death contributes to increased exposure, availability, and immunogenic characteristics of intracellular self antigens, which all participate in development of lupus autoimmunity. As our understanding of abnormalities of cell death in SLE advances, potential therapeutic opportunities await human implementation.

Purpose of reviewRenal involvement is a major cause of morbidity and mortality in systemic lupus erythematosus. In this review, we provide an update on recent discoveries in the pathogenesis, diagnosis, and treatment of lupus nephritis.
Recent findingsLocalized long-lived plasma cells have been ...

Purpose of reviewTo describe our current understanding of the role of T cells in the pathophysiology of systemic lupus erythematosus (SLE).
Recent findingsOver the last few years, the dominant role of T cells in autoimmunity and SLE was established. Genome-wide-association studies led to the dis...