Anti-CD80 monoclonal antibody, clone MEM-233 [R-PE]

Background:Glomerulopathies are the main cause of ESRD. Primary or secondary causes of glomerular diseases comprise more than 70% of cases that end up in renal replacement therapies.Summary:The total glomerular mass that each individual contains is key to maintaining normal kidney function. Diabetes, hypertension, and any primary or secondary glomerulopathy may threaten the normal glomerular function. In fact, any glomerular insult may alter the glomerular filtration barrier, which in turn is composed by the podocyte, the glomerular basement membrane, and the capillary endothelial cell. Deposition of immune complexes, antibodies, or complement components at the subepithelial, intramembranous, or subendothelial space, and mutations in podocyte, slit diaphragm, or glomerular basement membrane proteins or enzymes are the main etiologies of glomerular alterations. Podocytes are glomerular cells that do not divide under normal circumstances. In this respect, maintenance of the absolute podocyte number per glomer-ulus is critical for normal glomerular function. As the insult progresses, podocytes start to detach from the glomerular basement membrane. When the podocyte loss is over 40% in a glomerulus, glomerulosclerosis develops, and obliteration of the glomerulus is the rule. In clinical grounds, this phenomenon is diagnosed mainly by proteinuria and a decline in glomerular filtration rate.Key messages:In this review article, the impact of podocyturia in glomerular diseases and the main mechanisms of podocyte detachment are discussed. Finally, potential targets of therapeutic approach are suggested.

Myeloid-derived suppressor cells (MDSCs) are key regulators of immunity that initially have been defined by their ability to potently suppress T-cell responses. Recent studies collectively demonstrate that the suppressive activity of MDSCs is not limited to T cells, but rather affects a broad range of immune cell subsets. However, relatively few studies have assessed the impact of MDSCs on B cells, particularly in the human context. Here, we report that human monocytic MDSCs (M-MDSCs) significantly interfere with human B-cell proliferation and function in vitro. We further show that the inhibition occurs independent of direct cell-contact and involves the expression of suppressive mediators such as indoleamine 2, 3-dioxygenase (IDO), arginase-1 (Arg1), and nitric oxide (NO). In addition, our studies demonstrate that the suppression of B cells by M-MDSCs is paralleled by a skewing in B-cell phenotype and gene expression signatures. M-MDSCs induced the downregulation of key surface markers on activated B cells, including IgM, HLA-DR, CD80, CD86, TACI, and CD95. Concurrently, M-MDSCs but not conventional monocytes elicited alterations in the transcription of genes involved in apoptosis induction, class-switch regulation, and B-cell differentiation and function. In summary, this study expands our understanding of the regulatory role of M-MDSCs for human B-cell responses.