Abstract
Rheumatoid arthritis (RA) is caused by prolonged periodic interactions between genetic, environmental, and immunologic factors. Posttranslational modifications (PTMs) such as citrullination, carbamylation, and acetylation are correlated with the pathogenesis of RA. PTM and cell death mechanisms such as apoptosis, autophagy, NETosis, leukotoxic hypercitrullination (LTH), and necrosis are related to each other and induce autoantigenicity. Certain microbial infections, such as those caused by Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella copri, can induce autoantigens in RA. Anti-modified protein antibodies (AMPA) containing anti-citrullinated protein/peptide antibodies (ACPAs), anti-carbamylated protein (anti-CarP) antibodies, and anti-acetylated protein antibodies (AAPAs) play a role in pathogenesis as well as in prediction, diagnosis, and prognosis. Interestingly, smoking is correlated with both PTMs and AMPAs in the development of RA. However, there is lack of evidence that smoking induces the generation of AMPAs.
Highlights
Rheumatoid arthritis (RA), the most common form of chronic inflammatory arthritis, is mainly targeting synovial joints [1,2,3]
Valesini et al [46] hypothesized that citrullination in the lung could be an extra-articular factor in the origin of RA autoimmunogenicity that generates lung-resident autoreactive T cells, which migrate to other target organs by the upregulation of chemokine receptors—as in case of a rat model of autoimmune encephalitis [126]
There is a lack of evidence that smoking induces the production of autoantibodies; it correlates with the initiation of intolerance to multiple autoantigens, which may correlate with the overlapping of rheumatoid factor (RF), anticitrullinated protein/peptide antibodies (ACPAs), and anti-CarP
Summary
Rheumatoid arthritis (RA), the most common form of chronic inflammatory arthritis, is mainly targeting synovial joints [1,2,3]. The current strategy for RA treatment focuses on early and aggressive management before irreversible articular damage [7,9]. Rheumatism (EULAR) criteria are often used as the basis for a diagnosis of RA (Table 1). The 2010 ACR–EULAR criteria include anti-citrullinated protein/peptide antibodies (ACPAs) and rheumatoid factor (RF). The diagnostic criteria for ACPAs are the presentation of an early disease course and the prediction of an aggressive disease course [10]. Revised 2010 ACR–EULAR criteria consist of four domains: joint involvement, serologic study including RF and ACPAs, acute phase reactants (CRP and ESR), and duration of symptoms [10]. RA is the result of the interaction between numerous genetic, environmental, and immunological factors.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call