Lupus-derived monoclonal autoantibodies against apoptotic chromatin recognize acetylated conformational epitopes.

Objective: Nuclear components targeted by autoantibodies are a characteristic feature of the autoimmune disease systemic lupus erythematosus (SLE). The nucleosome, a major autoantigen, is released in patients with SLE as a result of a disturbed apoptosis and/or an insufficient clearance of apoptotic debris. During apoptosis the nucleosome is modified, thereby creating more immunogenic epitopes.

Apoptosis-induced histone H3 methylation is targeted by autoantibodies in systemic lupus erythematosus.

Objectives: In systemic lupus erythematosus (SLE) apoptotic chromatin is present extracellularly, which is most likely the result of disturbed apoptosis and/or insufficient removal. Released chromatin, modified during apoptosis, activates the immune system resulting in the formation of autoantibodies. A study was undertaken to identify apoptosis-induced histone modifications that play a role in SLE.

Comparison of three methods for isolation of urinary microvesicles to identify biomarkers of nephrotic syndrome.

Urinary microvesicles, such as 40-100 nm exosomes and 100-1000 nm microparticles, contain many proteins that may serve as biomarkers of renal disease. Microvesicles have been isolated by ultracentrifugation or nanomembrane ultrafiltration from normal urine; however, little is known about the efficiency of these methods in isolating microvesicles from patients with nephrotic-range proteinuria. Here we compared three techniques to isolate microvesicles from nephrotic urine: nanomembrane ultrafiltration, ultracentrifugation, and ultracentrifugation followed by size-exclusion chromatography (UC-SEC).

The tetraspanin CD37 protects against glomerular IgA deposition and renal pathology.

The tetraspanin protein CD37 is a leukocyte-specific transmembrane protein that is highly expressed on B cells. CD37-deficient (CD37(-/-)) mice exhibit a 15-fold increased level of immunoglobulin A (IgA) in serum and elevated numbers of IgA+ plasma cells in lymphoid organs. Here, we report that CD37(-/-) mice spontaneously develop renal pathology with characteristics of human IgA nephropathy.

Reactive oxygen species deglycosilate glomerular alpha-dystroglycan.

In the kidney, dystroglycan (DG) has been shown to cover the basolateral and apical membranes of the podocyte. alpha-DG is heavily glycosilated, which is important for its binding to laminin and agrin in the glomerular basement membrane. Furthermore, alpha-DG is negatively charged, which maintains the filtration slit open.