T cell responses to citrullinated self-peptides in patients with rheumatoid arthritis

Abstract

Antibodies to citrullinated peptides(ACPA) have high specificity for diagnosis and prognosis in rheumatoid arthritis (RA). ACPA are of IgG isotype and have an association with shared epitope-bearing HLA DR allele, suggesting that T cell help is needed for their generation. In mice models, T cell reactive to citrullinated self-peptide have been reported however, the human data is limited. Patients with RA satisfying ACR criteria were included and peripheral blood obtained for lymphoproliferative assay, antibody level and HLA typing. Citrullinated (Cit) and native peptides of Vimentin and Aggrecan were used for stimulating peripheral blood mononuclear cells in 5-day cultures. A SI value above >2.0 was taken as significant. HLA typing was done by SSCP and ACPA were tested by ELISA. A total of 50 patients (45 females; mean age 42 years; mean duration of disease 7 years) with RA were included in the study. A total of 90 % were RF positive and 78 % were ACPA positive. A total of 28 patients showed response to Agg peptide with 21 of them showing higher response to CitAgg as compared to native Agg peptide as well as the median SI was higher with CitAgg (6.07 Vs. 5.09; p = 0.009). A total of 31 patients showed response to Vim peptide with response to native peptide being higher than CitVim peptide in 22 of the patients. There was no association of T cell response with presence of shared epitope. Nearly half the patients with RA show T cell response to aggrecan and vimentin peptides; however, citrullination is not crucial for T cell response.