Citrullinated peptide and its relevance to rheumatoid arthritis: an update

Abstract

Citrullinated peptides in autoimmune diseases have been extensively studied in the last two decades. It is suggested that citrullination and the anti-citrullinated peptide antibodies (ACPA) plays a critical role in initiating inflammatory responses in autoimmune diseases, such as rheumatoid arthritis (RA). The most commonly accepted molecular mechanism for citrullinated peptides/proteins in RA is that the modified antigen resulting from cell damage or uncontrolled apoptosis could evoke an immune response leading to autoantibodies against these peptide or the whole protein. Citrullination of arginine is catalyzed by the enzyme peptidylarginine-deiminase (PAD) in the presence of calcium, changing the positively charged arginine to a polar but neutral citrulline. These citrullinated peptides/proteins and the relevant antibodies (ACPA) are important, not only in initiation of RA, but also in the diagnosis of the disease. In this evidence-based clinical review, we summarize recently published data on peptide citrullination and ACPA gauging the ability of anti-cyclic citrullinated peptide (anti-CCP) antibodies for diagnosis of RA. We also recapitulate results of studies elucidating the mechanism underlying the disease.

Posttranslational Modifications of Proteins in Type 1 Diabetes: The Next Step in Finding the Cure?

“…Citrullination, the deimidation of arginine to citrulline, has been implicated as a modification to autoantigens in RA (22) and multiple sclerosis (23) (Table 1). In RA, autoantibodies are generated against citrullinated joint autoantigens.…”

Apportioning Blame: Autoreactive CD4+ and CD8+ T Cells in Type 1 Diabetes

“…This process has been extensively described in celiac disease, where T cell recognition of gluten antigens strongly depends in the posttranslational deamination of Gln residues (Qiao et al 2011). Furthermore, the post-translational deimidation of Arg residues to citrulline has ben implicated in the generation of novel autoantigenic peptide epitopes in rheumatoid arthritis (Luban and Li 2010) and multiple sclerosis (Kidd et al 2008). In T1D evidence of similar post-translational modifications generating novel antigenic peptide epitopes has been scarce although CD4 T cell clones capable of recognizing a post-translationally modified peptide epitope derived from the insulin A chain have been described.…”

Prix Fixe: Efferocytosis as a Four-Course Meal

“…It is a systemic inflammatory disorder characterized by increased circulating autoantibodies against citrullinated peptides or the complement protein, C3 (Luban and Li 2010; Kenyon et al 2011). While there exists little direct evidence that rheumatoid arthritis is caused by defects in efferocytosis, site of inflammation often contain DAMPS, such as HMGB1 or histones H3 and H4, characteristic of uncleared apoptotic cells (Friggeri et al 2012).…”