Regulatory B Cells Are Reduced and Correlate With Disease Activity in Primary Membranous Nephropathy

Abstract

Introduction: Primary membranous nephropathy (PMN) is an autoimmune disease. Both T-regulatory cells (TREGs) and B-regulatory cells (BREGs) are decreased in patients with autoimmune disease. We evaluated the TREG and BREG population in patients of PMN treated with cyclical cyclophosphamide and steroid therapy (cCYC/GC).Methods: Twenty-four patients with PMN resistant to a restrictive strategy and treated with cCYC/GC therapy and 10 healthy controls were enrolled. The proteinuria, serum creatinine, and serum albumin were tested at monthly intervals and blood samples were collected before starting cCYC/GC and at 6 and 8 (2 months wash out) months of therapy. The peripheral blood mononuclear cells (PBMCs) after staining with fluorochrome-conjugated antibodies were then subjected to flow cytometric analysis for detection of TREGs (CD3þCD4þCD25hiCD127loFoxP3þ) and BREGs (CD19þCD5þCD1dhiIL10þ). TREGs and BREGs are presented as the percentage of T and B cells, respectively. Cases with remission at month 18 were classified as responders, and those without any remission as nonresponders.Results: Patients with PMN had a lower percentage of TREGs (P ¼ 0.07) and BREGs compared with healthy controls (P ¼ 0.0007). As compared with baseline, there was a significant increase in both BREGs (P ¼ 0.001) and TREGs (P ¼ 0.02) with the treatment (8 months). Patients who responded to therapy by 18 months had an increase in TREG (P ¼ 0.05) and BREG (P ¼ 0.0001) at month 8 compared with baseline. Conclusion:As compared with healthy controls, patients with PMN displayed a lower percentage of BREGs. Both TREGs and BREGs significantly improved with disease-specific therapy. BREGs had an association with clinical activity.

B Cells in Primary Membranous Nephropathy: Escape from Immune Tolerance and Implications for Patient Management

“…Meanwhile, there is conflicting evidence regarding the expression of Bregs, which usually regulate and suppress memory B cell development arising from T FH -B cell interactions, in the context of MN. Whereas some studies have suggested Bregs were decreased in patients with MN, and the population rose with successful treatment of MN, others showed higher concentrations of Bregs compared to healthy controls and patients with nonimmune causes of chronic kidney disease, though this may be a compensatory response rather than disease-causing per se [99,[110][111][112]. It is crucial to note that Bregs are composed of various B cell subpopulations, including CD19 + CD5 + CD1d hi cells that secrete IL-10, CD19 + CD5 + GzmB + cells that secrete granzyme B, as well as other classes of B cells, and that the limited studies looking at Bregs in MN have focused primarily on IL-10-secreting Bregs.…”

Circulating CD19 CD24hi CD38hi Regulatory B Cells Percentage in Lupus Nephritis Patients: Does It Differ?

“…B-lymphocytes cells are pathogenic in the majority of autoimmune disorders as they generate autoantibodies [19] . Recent researches have focused on Breg as a crucial functioning subset of B cells that has a vital capacity in suppressing the autoimmune response and have been widely studied in many autoimmune disorders including vasculitis, rheumatoid arthritis, multiple sclerosis, and SLE [20][21][22][23] . Wang et al [24] identified that Bregs augmented Treg cell expressions, which reduced inflammatory reactions in lupus-like mice.…”

Recent Advances in Clinical Diagnosis and Pharmacotherapy Options of Membranous Nephropathy in Iraqi Patients

“…Thrombospondin type-I domain-containing 7A is a multi-domain transmembrane protein expressed on podocytes with molecular weight of 250 kDa [1,39]. Its function is to increase the adhesion of cells.…”

“…Membranous nephropathy (MN), a glomerular disorder, is the most common cause of nephrotic syndrome in Caucasian individuals who do not have diabetes. The majority of MN cases are primary (idiopathic), while the remainder are related to systemic illness, pathogen exposure, or medications use [1]. Membranous nephropathy develops when the glomeruli, which are small blood capillaries in the kidney that are responsible for ultrafiltration of waste products and other polymers from the blood, suffer injury and thicken.…”