REGULATORY RHEUMATOID FACTOR IN RAT EXPERIMENTAL MODEL OF SJOGREN'S SYNDROME

Abstract

Earlier, we discovered a new factor of autoreactivity regulation called regulatory rheumatoid factor (regRF), which is represented by a population of anti-idiotype antibodies that have a common paratope specific to the PD1 molecule. RegRF has a cytotoxic effect on activated PD-1+CD4 T lymphocytes and controls the lymphocytes expansion. Its production during the induction period prevents experimental autoimmune diseases in rats. The association between regRF and resistance to the diseases suggests that regRF stimulation may be an effective treatment of autoimmune diseases. Sjögren's syndrome (SS) is an autoimmune disease that may follow other autoimmune diseases or occur independently. In SS, salivary gland (SG) lesions and lymphocytopenia may develop. It is not known whether the regulatory rheumatoid factor is a resistance factor to Sjögren's syndrome, and whether regRF stimulation can be used to treat this condition. The aim of this study was to clarify the role of regRF in ensuring resistance to Sjogrens syndrome in rats. SS was induced in Wistar rats through immunization with proteins isolated from mouse salivary glands. Blood samples were taken from the caudal vein each week before and after the immunization. Histological analysis of submandibular salivary gland tissue was performed 12 weeks after the initial immunization. Autoantibodies to CD4 were detected in serum by ELISA; regRF levels were measured by agglutination of IgG-coated erythrocytes; CD3, CD4 and CD8 lymphocyte counts were determined by flow cytometry in blood samples.

40% of rats immunized with mouse salivary gland proteins, salivary gland lesions typical of sialoadenitis occurring in Sjogren's syndrome have been detected. 50% of rats developed chronic CD3, CD4 and CD8 lymphocytopenia in response to immunization with mouse SG proteins. No autoantibodies to CD4 have been found in rats with CD4 lymphocytopenia. An association has been found between a high level of regulatory rheumatoid factor on day 7 following immunization with mouse salivary gland proteins and resistance to sialadenitis in rats. However, lymphocytopenia did not depend on regRF production during induction of Sjögren's syndrome. Thus, regulatory rheumatoid factor is a resistance factor to sialoadenitis, but not to lymphocytopenia in rat Sjogren's syndrome model.