Progress in Pathogenesis of Immunoglobin A Nephropathy

Abstract

The understanding of the pathogenesis of any disease is the key to effective and specific treatment of the disease. immunoglobulin A (IgA) nephropathy is an autoimmune disease of the kidney. Oxford MEST classification is commonly used to stratify patients according to the severity of the disease. Patients with IgA nephropathy seem to produce anti-GalNAc antibodies against a particularly defective IgA1. This immune complex deposits in the kidneys, leading to a type 3 hypersensitivity reaction which ultimately damages the kidneys. People of a certain genetic background and who experience upregulation of certain defective receptors seem to develop primary IgA nephropathy. Secondary IgA nephropathy could be due to dysbiosis of the microbiota in the gut, compromised gut immunity or other gut pathologies, pulmonary function abnormalities, or amyloidosis. Overproduction of IgA due to plasma cell dyscrasia or reduced clearance of IgA due to liver abnormalities could also be potential causes. Genes that predispose individuals to IgA nephropathy and intestinal abnormalities, such as Celiac disease, seem to overlap and these people tend to have a poorer prognosis and need to be placed on more intensive treatment regimens. IgA Vasculitis seems to be a systemic form of IgA nephropathy, whereby IgA deposits systemically and leads to multiple disease manifestations. Patients in high-risk groups could also be prophylactically screened for the disease and closely monitored by immunohistochemical methods such as an enzyme-linked immunosorbent assay (ELISA) or identified by genetic testing. Currently, the major treatment regimens involve supportive therapy or immunosuppressive therapy which has major side effects. More specific treatment methods such as monoclonal antibodies, immunoglobulin replacement therapy, or low-antigen-content diet could also be looked into as potential treatment options. Stem cell replacement, by way of bone marrow transplant and tonsillectomy, has been suggested as a treatment option in patients with indications.

Efficacy and Safety of Glycosides of Tripterygium wilfordii Combined with Renin-Angiotensin System in the Treatment of IgA Nephropathy: A Systematic Review and Meta-Analysis

“…IgA nephropathy (IgAN), also known as Berger's disease, is divided into two categories: primary and secondary. Primary IgA nephropathy is more common, accounting for about 36.7% to 58.2% of primary glomerular diseases diagnosed by renal pathology in China, and its incidence has been gradually increasing in recent years [1,2]. It can be seen at any age, and patients aged 16-35 years account for about 80% of the total number of patients with the disease [3,4].…”

Efficacy and safety of leflunomide combined with corticosteroids for the treatment of IgA nephropathy: a Meta-analysis of randomized controlled trials

“…Besides, leflunomide was also shown to inhibit the activity of dihydrofolate dehydrogenase and cell cycle-dependent kinases, further preventing the proliferation of T and B lymphocytes and immune responses [ 46 ]. In view of the importance of autoimmunity in the pathogenesis of IgAN, leflunomide could also confer its therapeutic efficacy for IgAN as an immunosuppressant [ 47 ]. In addition, some studies also suggested a possible direct benefit of leflunomide on glomerular disease.…”

Unraveling chronic kidney disease in children: a surprising manifestation of celiac disease

“…However, with early diagnosis and treatment, most people with IgA nephropathy can live a normal life ( 36 ). The link between a dysregulated gut-associated lymphoid tissue (GALT) and IgAN was hypothesized following the observation of a higher association between IgA nephropathy and celiac disease ( 37 ). However, in people with IgAN, GALT can become dysregulated, leading to the production of abnormal IgA antibodies.…”