Xin Tian1, Yi Zhao, Zhan-Guo Li. 1. Department of Pediatrics, Second Hospital of Jilin University, Changchun 130041, China.
Abstract
OBJECTIVE: To investigate the T cell proliferative response and antibody formation to citrullinated collagen type II (Cit-CII) in patients with rheumatoid arthritis (RA), and explore whether autoreactive T cells responding to Cit-CII plays a role in the pathogenesis of RA. METHODS: Arginine residues of bovine collagen type II (CII) were converted to citrulline residues by peptidylarginine deiminase (PAD). Peripheral blood samples were collected from 34 RA patients, and 18 sex- and age-matched controls, including 6 osteoarthritis patients and 12 healthy blood donors. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured with Cit-CII, CII, or fetal bovine serum RPMI 1640 fluid, phytohemagglutinin (PHA), or citrullinated buffer as controls. Cellular reactivity levels against Cit-CII and CII were investigated by measuring the proliferation of PBMCs to calculate the stimulation index (SI). ELISA was used to detect the presence of antibodies against Cit-CII and CII. RESULTS: The positive rate of T cell proliferative response to Cit-CII of the RA group was 32.4% (11/34), significantly higher than that of the control group (0, P < 0.05). The positive rate of T cell proliferative response to CII of the RA group was 35.3% (12/34), significantly higher than that of the control group (11.1%, P < 0.05). Interestingly, Cit-CII could not elicit a better T cell proliferative response than CII did. In the RA patients, the anti-Cit-CII antibody positive rate was 52.9% (18/34), significantly higher than that of the anti-CII antibody positive rate [32.4% (11/34), P < 0.05). The serum IgG anti-CII antibody positive rate of the patients with positive T cell responses to CII was 58.3% (7/12), significantly higher than that of the patients with negative T cell responses to CII [18.2% (4/22), P < 0.05]. The serum IgG anti-CII antibody positive rate of the patients with positive T cell responses to Cit-CII was 72.7% (8/11), significantly higher than that of the patients with negative T cell responses to Cit-CII [43.5% (10/23), P < 0.05]. CONCLUSION: The recognition of Cit-CII by circulating IgG antibodies is a RA-specific serological phenomenon. The formation of CII antibody in the RA patients may be related to B cell activation mediated by CII specific T cells. The role of Cit-CII in RA cellular immune need be further studied.
OBJECTIVE: To investigate the T cell proliferative response and antibody formation to citrullinated collagen type II (Cit-CII) in patients with rheumatoid arthritis (RA), and explore whether autoreactive T cells responding to Cit-CII plays a role in the pathogenesis of RA. METHODS:Arginine residues of bovine collagen type II (CII) were converted to citrulline residues by peptidylarginine deiminase (PAD). Peripheral blood samples were collected from 34 RA patients, and 18 sex- and age-matched controls, including 6 osteoarthritispatients and 12 healthy blood donors. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured with Cit-CII, CII, or fetal bovine serum RPMI 1640 fluid, phytohemagglutinin (PHA), or citrullinated buffer as controls. Cellular reactivity levels against Cit-CII and CII were investigated by measuring the proliferation of PBMCs to calculate the stimulation index (SI). ELISA was used to detect the presence of antibodies against Cit-CII and CII. RESULTS: The positive rate of T cell proliferative response to Cit-CII of the RA group was 32.4% (11/34), significantly higher than that of the control group (0, P < 0.05). The positive rate of T cell proliferative response to CII of the RA group was 35.3% (12/34), significantly higher than that of the control group (11.1%, P < 0.05). Interestingly, Cit-CII could not elicit a better T cell proliferative response than CII did. In the RA patients, the anti-Cit-CII antibody positive rate was 52.9% (18/34), significantly higher than that of the anti-CII antibody positive rate [32.4% (11/34), P < 0.05). The serum IgG anti-CII antibody positive rate of the patients with positive T cell responses to CII was 58.3% (7/12), significantly higher than that of the patients with negative T cell responses to CII [18.2% (4/22), P < 0.05]. The serum IgG anti-CII antibody positive rate of the patients with positive T cell responses to Cit-CII was 72.7% (8/11), significantly higher than that of the patients with negative T cell responses to Cit-CII [43.5% (10/23), P < 0.05]. CONCLUSION: The recognition of Cit-CII by circulating IgG antibodies is a RA-specific serological phenomenon. The formation of CII antibody in the RA patients may be related to B cell activation mediated by CII specific T cells. The role of Cit-CII in RA cellular immune need be further studied.