CTLA4 polymorphisms in minimal change nephrotic syndrome in children: A case-control study

摘要

The pathogenesis of minimal change nephrotic disease (MCD) remains unknown. Several studies showed elevated levels of cy-tokines (EL-1, IL-2, soluble IL-2R, IL-4, IL-12, DL-18, IL-13; TNF-alpha, IFN-y), which are mainly produced by lymphocytes, in the serum of patients with MCD. Circulating factors contribute to podocyte injury, resulting in enhanced CD80 expression and accompanying proteinuria. Immunosuppressive drugs are the major treatment option, which suggests either involvement of the immune system or a direct effect on podocytes in MCD. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), which is expressed mainly on T lymphocytes but recently was found to be expressed on podocytes also, represents an essential negative regulator of the immune system. CTLA4 appears to play a role in a number of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, Graves disease, and multiple sclerosis. Like CD28, CTLA4 is a cell-surface coreceptor on T cells that binds CD80/CD86 on antigen-presenting cells. In contrast to CD28, CTLA4 acts in an antagonistic manner and prevents T-cell activation.