Regulatory rheumatoid factor in rat model of Sjogren’s syndrome

Earlier, we have revealed a novel factor regulating autoreactivity called regulatory rheumatoid factor (regRF), which is represented by a population of anti-idiotypic antibodies that have a common paratope specific to the PD1 molecule. RegRF exerts cytotoxic effect on activated PD-1+CD4 T lymphocytes and controls the lymphocyte expansion. Its production during the induction period prevents experimental autoimmune diseases in rats. The association between regRF and resistance to these disorders suggests that regRF stimulation may be an effective treatment of autoimmune diseases. Sjögren’s syndrome (SS) is an autoimmune disease that may accompany other autoimmune diseases or occur independently. Salivary gland (SG) lesions and lymphocytopenia may develop in SS. It is not known whether the regRF is a resistance factor to SS, and if the regRF stimulation may 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 by immunization with proteins isolated from murine SG. Blood samples were taken from the caudal vein each week before and after the immunization. Histological analysis of submandibular SG 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 SG proteins, have developed SG lesions typical of sialoadenitis occurring in Sjogren’s syndrome. 50% of rats exhibited chronic lymphocytopenia (CD3, CD4 and CD8 cell populations) in response to immunization with mouse SG proteins. In rats with CD4 lymphocytopenia, no autoantibodies to CD4 have been found. An association has been found between a high level of regRF on day 7 following immunization with mouse SG proteins and resistance to sialadenitis in rats. However, lymphocytopenia did not depend on regRF production during induction of SS. Thus, regulatory rheumatoid factor is a preventive factor for sialoadenitis, but not to lymphocytopenia in rat model of Sjogren’s syndrome.