The Role of Immune Modulation in Pathogenesis of IgA Nephropathy

Abstract

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with diverse clinical manifestations characterized by recurrent gross hematuria or microscopic hematuria, and pathological changes featuring poorly O-galactosylated IgA1 deposition in the glomerular mesangium. Pathogenesis has always been the focus of IgAN studies. After 50 years of research, most scholars agree that IgAN is a group of clinicopathological syndromes with certain common immunopathological characteristics, and multiple mechanisms are involved in its pathogenesis, including immunology, genetics, and environmental or nutritional factors. However, the precise pathogenetic mechanisms have not been fully determined. One hypothesis about the pathogenesis of IgAN suggests that immunological factors are engaged in all aspects of IgAN development and play a critical role. A variety of immune cells (e.g., dendritic cells, NK cells, macrophages, T-lymphocyte subsets, and B-lymphocytes, etc.) and molecules (e.g., IgA receptors, Toll-like receptors, complements, etc.) in innate and adaptive immunity are involved in the pathogenesis of IgAN. Moreover, the abnormality of mucosal immune regulation is the core of IgAN immunopathogenesis. The roles of tonsil immunity or intestinal mucosal immunity, which have received more attention in recent years, are supported by mounting evidence. In this review, we will explore the latest research insights on the role of immune modulation in the pathogenesis of IgAN. With a better understanding of immunopathogenesis of IgAN, emerging therapies will soon become realized.

Dysbiosis in the Salivary Microbiome Associated with IgA Nephropathy—‍A‍ ‍Japanese Cohort Study

“…Even though P. melaninogenica has been identified as a member of the Japanese salivary core microbiome (Takeshita et al, 2016), previous studies implicated it in the development of oral and systemic diseases (Brook, 1995;Sibley et al, 2011;Kondo et al, 2018). The expression of TLR2 was previously shown to be up-regulated in the blood mononuclear cells of IgAN patients (Chang and Li, 2020;Saito et al, 2016) and in the dendritic cells of IBD patients (CD and UC) (Hug et al, 2018). Since P. melaninogenica reportedly stimulates cytokine responses via TLR2 pathways (Kondo et al, 2018), it has the potential to contribute to the progression of inflammatory disorders, such as UC and IgAN.…”

Zhen-Wu-Tang Protects IgA Nephropathy in Rats by Regulating Exosomes to Inhibit NF-κB/NLRP3 Pathway

“…Multiple factors are involved in the pathogenesis of IgAN. When circulating complexes deposit in the glomeruli, the GMCs are activated, followed by cell proliferation and excessive production of inflammatory factors that promote impaired renal function (Chang and Li, 2020). As a new kind of biological marker, exosomes can not only mediate intercellular communication in inflammation but also remove waste or harmful components, which participate in the development of many renal deseases (Li Q. et al, 2019).…”

TGF-β1 Signaling: Immune Dynamics of Chronic Kidney Diseases

“…Autoantibodies production by B-cells is crucial for the development of IgA nephropathy and lupus nephritis. In the pathogenesis of IgA nephropathy, B-cells produce aberrant galactosylated IgA and its autoantibodies (anti-glycan antibodies) to form immune complexes, which deposition on mesangial cells to initiates glomerulonephritis and subsequent CKD progression ( 77 – 79 ). Similarly, in Lupus nephritis, multiple autoantibodies were involved in the immune complexes formation, including anti-dsDNA ( 80 ), anti-C1q ( 81 ), and anti-nucleosome ( 82 ) autoantibodies.…”