%0 Journal Article
%T T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles
%A Soi Law
%A Shayna Street
%A Chien-Hsiung Yu
%A Christelle Capini
%A Sakoontalla Ramnoruth
%A Hendrik J Nel
%A Eline van Gorp
%A Claire Hyde
%A Kim Lau
%A Helen Pahau
%A Anthony W Purcell
%A Ranjeny Thomas
%J Arthritis Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/ar3848
%X We compared T-cell proliferative and cytokine responses to citrullinated and native type II collagen 1,237 to 1,249, vimentin 66 to 78, aggrecan 84 to 103 and fibrinogen 79 to 91 in six SE+ healthy controls and in 21 RA patients with varying disease duration. Cytokine-producing cells were stained after incubation with peptide in the presence of Brefeldin-A.Although proliferative responses were low, IL-6, IL-17 and TNF were secreted by CD4+ T cells of SE+ RA patients and healthy controls, as well as IFN¦Ã and IL-10 secreted by RA patients, in response to citrullinated peptides. Of the epitopes tested, citrullinated aggrecan was most immunogenic. Patients with early RA were more likely to produce IL-6 in response to no epitope or to citrullinated aggrecan, while patients with longstanding RA were more likely to produce IL-6 to more than one epitope. Cytokine-producing CD4+ T cells included the CD45RO+ and CD45RO- and the CD28+ and CD28- subsets in RA patients.Proinflammatory cytokines were produced by CD4+ T cells in SE+ individuals in response to citrullinated self-epitopes, of which citrullinated aggrecan was most immunogenic. Our data suggest that the T-cell response to citrullinated self-epitopes matures and diversifies with development of RA.Rheumatoid arthritis (RA) is an autoimmune disease characterised by inflammation of joint synovial tissue and deformity and destruction of associated bone, cartilage and soft tissues. Several autoantigens are described in RA, including a variety of proteins that become citrullinated in diseased joints. Citrullination is a physiological process of arginine deimination that occurs during apoptosis and inflammation. This process results in modification of arginine-containing proteins, which can give rise to sets of neo-self-antigens in individuals bearing at-risk HLA alleles [1].Specific HLA-DR gene variants mapping to amino acids 70 to 74 of the third hypervariable region of DR¦Â chains are highly associated with RA [2]. This reg
%U http://arthritis-research.com/content/14/3/R118