What are the pathogenesis of IgA nephritis?2017-05-06 17:59
The pathogenesis of this disease has not been clarified. Because of the deposition of IgA in the skin and liver of the patient, it is suggested that it is a systemic disease. Because of the presence of granular IgA and C3 deposition in the glomerular mesangial area and capillaries, it is suggested that the pathogenesis of immune complex. At present, the study is focused on the ability of the antigen to pass through the mucosa and the defects of the mucosal barrier, whether the IgA structure is defective and the immune regulatory function is defective. Previous studies have suggested that the deposition of IgA may be a source of mucosal origin. However, recent studies using highly specific technology, this disease is confirmed by the deposition of IgA1, is the main source of the system, mainly produced by bone marrow and lymph system; mucosa derived IgA2 IgA deposition is mainly seen in hepatic glomerular sclerosis in. In patients with the disease can also be seen in the circulation of total IgA1 and IgA1 containing immune complexes increased in the bone marrow IgA1 cells and the formation of a large number of poly. The J chain can be found in the kidney tissue of the disease, so it is suggested that the IgA is a poly, and the secretory block is very rare. However, the available information is not yet able to determine the source of the IgA deposits in the disease.
Many antigens, including a variety of viruses and a variety of food antigens can be detected in the patient's mesangial area, and often accompanied by IgA1 deposition. Antibodies to these antigens are also IgA1. Since these antibodies may also be present in the circulation of normal subjects, the antigens are not specific or characteristic.
There is evidence that the disease has abnormal immune regulation. The IgA1 circulating immune complex of the disease was found to have a poly IgA1 rheumatoid factor. The IgG antibody against the heavy chain Fab fragment was increased and the IgM antibody was decreased. Interestingly, there was a similar anti immunoglobulin pattern in HIV infected individuals, but there was no renal IgA deposition. This suggests that the presence of autoantibodies alone is not the cause of mesangial IgA deposition. In addition, two anti endothelial cell autoantibodies (IgG) were found. C3 deposition in renal tissue of this disease suggests that activated complement pathway. However, IgA itself does not have the ability to activate complement, while the IgA immune complex can activate the complement pathway, but its ability to bind to complement and C3b is weak. It is generally believed that the complement activation and the formation of membrane attack complex in the kidney, the need for IgG-IgA complex, but there are IgA and C3 deposition in renal tissue and no IgG or IgM deposition is very common. Therefore, the mechanism of complement activation is unclear. Cellular immunity is also involved in the pathogenesis. This disease has been found to be a helper T cell (CD4) increased and T suppressor cells (CD8) decreased; with the conversion of IgM synthesis for IgA synthesis of Ta4 cells increased, the frequency associated with the Sa1 allele also increased; caused by same IgA type conversion of TGF beta, IgA promote B lymphocyte differentiation the IL-5 and IgA mediated IL-4 formation have increased. Although both T cells and B cells are involved in the process of IgA synthesis, the increased IgA synthesis is not the cause of IgA deposition in the mesangial area, because of the presence of IgA deposition in patients with multiple myeloma (IgA). Therefore, structural immunological / physical and chemical abnormalities may be the cause of IgA deposition.
The polyclonal antibody against bovine serum albumin can be detected in serum and mesangial cells. Recently, some people use obtained from patients of renal cortex and the glomerular IgA obtained 5 monoclonal antibody gene, and their serum or plasma cell response is poor, and the kidney has a high response rate, suggesting that the kidney is deposited with the polyclonal antibody of IgA abnormal properties. In addition, IgA1 1, 3- galactose transferase deficiency was found in the patients, and the clearance rate of IgA1 or IgA1 was changed, which resulted in the deposition of mesangial cells.
In summary, the deposition of antigen, with or without a cell-mediated immune response, mesangial cell IgA complex formation speed and with the IgAFc receptor or neutrophil clearance in the pathogenesis and mechanism of cytokines and growth factors are mainly involved in mesangial proliferation and atherosclerosis.