Decreased IL-10(+) regulatory B cells (Bregs) in lupus nephritis patients.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell-dependent autoantibody production. Recently, a new B-cell subset was discovered that has a regulatory capacity. The aim of this study was to analyse regulatory B cells (Bregs) in SLE patients. METHOD: Peripheral mononuclear blood cells (PBMCs) of 34 SLE patients fulfilling the American College of Rheumatology (ACR) criteria for SLE and 21 healthy controls (HC) were included. PBMCs were stained for CD19, CD24, and CD38 and analysed by flow cytometry. In vitro stimulated PBMCs with CpG and restimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin were investigated for IL-10(+) Bregs . RESULTS: The percentages of circulating CD19(+)CD24(hi)CD38(hi) cells in HC were not different those in from SLE patients. The percentages of IL-10(+) Bregs were significantly decreased in SLE patients, in particular those with lupus nephritis (LN), compared to HC. The proportion was independent of disease activity. CONCLUSIONS: This is the first study to demonstrate a decrease in IL-10-producing B cells in LN patients compared to HC, reflecting an impaired regulatory function.

mTOR-understanding the clinical effects.

The target of rapamycin (TOR) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress. The TOR kinase, which was originally discovered in yeast, is also expressed in human cells as mammalian TOR (mTOR). In this review, we focus on how mTOR-inducible signals function in cell protection and cell survival of effector and regulatory T cells as well as its role in endothelial cell biology. We evaluate how signaling is important for vascular endothelial cell growth, survival, and proliferation; and we consider how the function of mTOR in endothelial cells may be clinically important in the rejection process. Understanding the biology of mTOR allows clinicians to use mTOR inhibitors optimally as therapeutics following solid organ transplantation.

Immigrating progenitor cells contribute to human podocyte turnover.

Podocyte depletion is a critical event in glomerular diseases in general and in the development of focal segmental glomerulosclerosis in particular. Progenitor cell immigration is a possible mechanism of podocyte replacement for the preservation of nephron function since, with rare exception, mature podocytes are thought to be incapable of replication. We examined eight paraffin-embedded renal biopsies from six male recipients of female transplant kidneys for receiver-derived podocytes. Fluorescent in situ hybridization for the Y chromosome was combined with immunofluorescence for the podocyte marker, Wilms tumor-1 antigen. Recipient-derived podocytes were found in 4 of 8 biopsies representing 3 of the 6 patients. Overall, 5 of the 740 podocytes examined in the female-donated kidneys were male derived. Our study suggests that immigrating progenitor cells are able to replace podocytes in humans; however, the importance of this process in physiologic and pathologic conditions is unknown.