[T cell proliferative response and antibody formation to citrullinated collagen type II in patients with rheumatoid arthritis].
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].


CONCLUSIONS
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.
Tian
Xin
X
Department of Pediatrics, Second Hospital of Jilin University, Changchun 130041, China.
Zhao
Yi
Y
Li
Zhan-Guo
ZG
D000328:Adult; D000368:Aged; D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D002956:Citrulline / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D024043:Collagen Type II; D002956:Citrulline