As BAFF is able to induce CSR, the intestinal immunoglobulins may well be of another isotype than IgE. The results indicate that BAFF might be particularly involved in non-IgE-mediated reactions. Determination of BAFF levels in different body fluids, as in gut lavage fluid in our study, thus
supports the notion that BAFF is produced locally in different compartments of the body, not only in joints and airways but also in the gut, in response to inflammation and allergic reactions. In addition, our study raises the possibility that Adriamycin delayed-type hypersensitivity reactions to food may result from a unique immunoglobulin class switching in the intestine. Enhanced BAFF expression has been noted in several viral infections such as in human immunodeficiency virus (HIV), Epstein–Barr virus (EBV) and hepatitis C virus (HCV) infections [45–47]. Studies in patients with HIV suggest that these patients have increased levels of BAFF and IL-10 in their serum, and BAFF concentration increased with disease progression [45, 46]. EBV-infected
B cells have been shown to express BAFF [4, 47]. In patients with HCV, increased BAFF levels in serum were associated with the presence of arthritis/arthralgia and/or vasculitis, and high values at onset of acute HCV infection can predict its evolution to chronic infection . Another https://www.selleckchem.com/products/MK-2206.html significant association was found between increased serum BAFF levels and liver fibrosis in HCV-infected patients, showing that patients with cirrhosis have more BAFF expression than non-cirrhotic patients [49, 50]. B-cell expansion and lymphoproliferation are common features in patients chronically infected with HCV . Induction of BAFF expression during HIV, EBV PARP inhibitor and HCV infections may explain the connection
between viral infections and the occasional development of autoimmunity. Persistent viral infection may enhance cell apoptosis and the release of various nuclear antigens including heat shock proteins and the binding of toll-like receptors (TLRs) [52, 53]. Following such activation, dendritic cells become overactivated and increase their production of proinflammatory cytokines, one of which is BAFF, which may terminate B-cell tolerance and stimulate autoreactive B cells to produce autoantibodies. Neoplastic B cells express one or more of the receptors for BAFF on their surface, and impaired TACI upregulation contributes to hyperactive B cells and cancer development [3, 4]. In addition to autoimmune and allergic diseases, high BAFF levels were demonstrated in the serum of patients with B-cell chronic lymphocytic leukaemia (CLL), multiple myeloma and non-Hodgkin’s lymphoma [54–57]. One study showed that many patients had increased levels of BAFF on circulating CLL compared with non-transformed B cells . In different types of non-Hodgkin’s lymphoma, BAFF concentrations were at least threefold higher in serum of patients with follicular lymphoma [56, 58].