Regulatory B cells (Breg) are widely regarded as immunomodulatory cells which play an immunosuppressive role. Breg inhibits pathological autoimmune response by secreting interleukin‐10 (IL‐10), transforming growth factor‐ β (TGF‐ β ), and adenosine and through other ways to prevent T cells and other immune cells from expanding. Recent studies have shown that different inflammatory environments induce different types of Breg cells, and these different Breg cells have different functions. For example, Br1 cells can secrete IgG4 to block autoantigens. Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the humoral immune response is dominant and the cellular immune response is impaired. However, only a handful of studies have been done on the role of Bregs in this regard. In this review, we provide a brief overview of the types and functions of Breg found in human body, as well as the abnormal pathological and immunological phenomena in IMN, and propose the hypothesis that Breg is activated in IMN patients and the proportion of Br1 can be increased. Our review aims at highlighting the correlation between Breg and IMN and proposes potential mechanisms, which can provide a new direction for the discovery of the pathogenesis of IMN, thus providing a new strategy for the prevention and early treatment of IMN.

Membranous nephropathy (MN) is an organ-restricted autoimmune disease mainly caused by circulating autoantibodies against podocyte antigens, including the M-type phospholipase A2 receptor (PLA2R) and thrombospondin domain-containing 7A (THSD7A). Antibodies against PLA2R are present in 70%–80% and against THSD7A in 2% of adult patients, which provides a paradigm shift in molecular diagnosis and management monitoring. Both antigens share some similar characteristics: they are expressed by podocytes and have wide tissue distributions; they are bound by autoantibodies only under nonreducing conditions, and the subtype of most autoantibodies is IgG4. However, the factors triggering autoantibody production as well as the association among air pollution, malignancy, and the pathogenesis of MN remain unclear. In this review, we discuss the similarity between the pathological mechanisms triggered by disparate antigens and their associated diseases. Furthermore, we demonstrated the possibility that PM2.5, malignancy, and gene expression specifically induce exposure of these antigens through conformational changes, molecular mimicry, or increased expression eliciting autoimmune responses. Thus, this review provides novel insights into the pathological mechanism of MN.

Background: Patients undergoing hemodialysis (HD) for chronic kidney disease (CKD) often encounter anemia. Roxadustat has not only undergone phase II-III clinical trials in patients suffering from CKD and undergoing HD; a number of post-marketing clinical studies have been conducted using the drug. This article was to assess the effectiveness and safety of roxadustat in managing anemia among patients with CKD undergoing HD. Methods: A thorough search was performed across eight databases, including PubMed, Web of Science, Cochrane Library, Embase, Wan Fang, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQ VIP), and SinoMed to identify randomized clinical trials (RCTs) examining the effectiveness and safety of roxadustat in managing anemia among individuals suffering from CKD and undergoing HD. This search included studies from the inception of these databases to April 2023. Results: Two phase II, one phase III, and 16 post-marketing studies with 1688 participants were included. Serum iron (SI), transferrin, and total iron-binding capacity (TIBC) levels changed from baseline (∆SI, ∆transferrin, and ∆TIBC) and were significantly more increased for roxadustat than for erythropoiesis-stimulating agents (ESAs): MD 2.55, (95% CI 1.51 to 3.60), p < 0.00001; MD 0.55, (95% CI 0.41 to 0.69), p < 0.00001; and MD 6.54, (95% CI 4.50 to 8.59), p < 0.00001, respectively. Roxadustat was not inferior to ESAs with regard to increasing Hb (∆Hb) levels [MD 1.17 (95% CI 0.71 to 1.63), p < 0.00001] (g/dL). No statistically significant distinctions of the ∆ferritin, ∆hepcidin, and transferrin saturation (TSAT) from baseline (∆TSAT) level were identified between roxadustat and ESAs. C-reactive protein (CRP) levels changed from baseline (∆CRP) and were significantly more reduced for roxadustat than for ESAs. As for safety, the analysis indicated no notable difference in the occurrence of adverse events (AEs) and serious adverse events (SAEs) between roxadustat and ESAs. Conclusions: This meta-analysis demonstrated that roxadustat outperformed ESAs in enhancing SI, transferrin, and TIBC levels while also decreasing CRP levels. Roxadustat was not inferior to ESAs in terms of improving Hb levels and safety. These findings suggest that roxadustat was well tolerated and a potent alternative to ESAs in managing anemia among patients suffering from CKD and undergoing HD.