B cells in type 1 diabetes mellitus and diabetic kidney disease

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder that affects an estimated 30 million people worldwide. It is characterized by the destruction of pancreatic β cells by the immune system, which leads to lifelong dependency on exogenous insulin and imposes an enormous burden on patients and health-care resources. T1DM is also associated with an increased risk of comorbidities, such as cardiovascular disease, retinopathy, and diabetic kidney disease (DKD), further contributing to the burden of this disease. Although T cells are largely considered to be responsible for β-cell destruction in T1DM, increasing evidence points towards a role for B cells in disease pathogenesis. B cell-depletion, for example, delays disease progression in patients with newly diagnosed T1DM. Loss of tolerance of islet antigen-reactive B cells occurs early in disease and numbers of pancreatic CD20 B cells correlate with β-cell loss. Although the importance of B cells in T1DM is increasingly apparent, exactly how these cells contribute to disease and its comorbidities, such as DKD, is not well understood. Here we discuss the role of B cells in the pathogenesis of T1DM and how these cells are activated during disease development. Finally, we speculate on how B cells might contribute to the development of DKD.

B Cell Responses: Cell Interaction Dynamics and Decisions

“…B cell depletion therapy has also been efficacious in several other autoimmune diseases, including multiple sclerosis (MS), type 1 diabetes, and rheumatoid arthritis (RA) (Smith et al, 2017;Townsend et al, 2010). While the potential contributions of autoantibodies to the pathology of these diseases are still being explored, autoantigen presentation has been posited as another mechanism for B cell disease-promoting activity.…”

T-Cell–Specific PTPN2 Deficiency in NOD Mice Accelerates the Development of Type 1 Diabetes and Autoimmune Comorbidities

“…Peer Review Only Diabetes also the recruitment of B220 + B cells, which promote the expansion and activation of T cells targeting  cell antigens(41). Therefore, another mechanism by which PTPN2 deficiency might influence disease progression in NOD mice is through effects on the B cell compartment.…”

Prevalence of nephropathy in type 1 diabetes in the Arab world: A systematic review and meta‐analysis

“…Full‐text articles were screened to capture the relevant data for patients with T1D who had DN without age limits (Table ). Our inclusion criteria were as follows: Article was published as a peer‐reviewed research article, patients developed DN as a complication of T1D only, patients were of Arab ethnicity and lived in Arab countries, and patients developed nephropathy as measured by microalbuminuria or macroalbuminuria or by reduced glomerular filtration rate. Our exclusion criteria were as follows: It was unclear whether patients developed nephropathy because of T1D or T2D, nephropathy resulted from T2D only, the type of diabetes was not mentioned in the study, lack of random selection of the T1D subjects, and publication in a language other than English.…”

“…The exact cause of T1D is still unknown. T cells are largely considered to be responsible for β cell destruction; however, increasing evidence points toward a role for B cells in disease pathogenesis . Diabetic nephropathy (DN) is 1 of the most serious complications among patients with T1D.…”

“…T cells are largely considered to be responsible for β cell destruction; however, increasing evidence points toward a role for B cells in disease pathogenesis. 1 Diabetic nephropathy (DN) is 1 of the most serious complications among patients with T1D. Although hyperglycaemia is considered to be 1 of the major risk factors in the development of DN, the pathogenesis process that is involved in the development of DN involves many other factors that are not limited to hyperglycaemia.…”