Gingival tissue, an extrasynovial source of malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins

Abstract

Background and Objective Postranslational modification of proteins can lead to the production of autoantibodies and loss of immune tolerance. This process has been hypothesised to be a critical factor in the pathogenesis of rheumatoid arthritis. The objective of this study was to demonstrate that inflamed human gingival tissue provides an extrasynovial source of malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins all of which are considered to be linked to the development of rheumatoid arthritis. Identification of such modified proteins in inflamed gingiva may explain, in part, how inflammation of the periodontal tissues may influence the development of rheumatoid arthritis. Material and Methods Gingival biopsies of healthy, mild and moderate periodontitis were triple stained with antibodies against malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins. Results Assessment of healthy gingival tissue revealed negligible staining for carbamylated, malondialdehyde‐acetaldehyde (MAA), or citrullinated proteins. Mild periodontitis was positive for all three modifications. Furthermore, there was an increase in staining intensity for carbamylated, citrullinated and MAA‐modified proteins in moderate periodontitis. Negative staining results were observed for the isotype controls. Conclusion This study provides evidence for the presence of citrullinated, carbamylated and MAA adduct modified proteins in inflamed periodontal tissues. The potential for these proteins to play a role in autoimmunity in a multi‐system inflammatory syndromic disease model now needs to be determined.

Circulating levels of carbamylated protein and neutrophil extracellular traps are associated with periodontitis severity in patients with rheumatoid arthritis: A pilot case-control study

“…Interestingly, the results of the current study also indicated that the patients with only periodontitis had significantly higher circulating levels of CarP than the controls, which is supported by the findings of another study that showed the presence of CarP in inflamed periodontal tissue [ 17 ]. However, the serum NETs levels were comparable between the patients with periodontitis and controls in the present study.…”

“…Experimental arthritis studies have also shown that the appearance of anti-CarP antibodies in the sera precedes the onset of RA [ 15 , 16 ]. Recently, the presence of CarP was also demonstrated in inflamed periodontal tissue from patients with mild to moderate periodontitis [ 17 ]. These findings led to the hypothesis that protein carbamylation in patients with RA may also be shared by periodontitis.…”

The P. gingivalis Autocitrullinome Is Not a Target for ACPA in Early Rheumatoid Arthritis

“…However, while our data support the notion that this autocitrullinome does not act as a trigger of initial ACPA production as occurs during early stages of RA, we cannot rule out that autocitrullinated P. gingivalis proteins may contribute to autoimmune responses during later stages of disease (Kudo-Tanaka et al 2007). Moreover, host-derived inflammatory cues, as may arise during periodontitis that is driven by P. gingivalis or other oral pathobionts but also nonmicrobial factors (Curtis et al 2011), may induce posttranslational protein modifications, including citrullination and carbamylation (Bright et al 2018), and thus could be a mechanism linking periodontitis and RA.…”

Salivary IgA to MAA-LDL and Oral Pathogens Are Linked to Coronary Disease

“…OxLDL plays a key role in the inflammation of arterial wall and atherogenesis. Oxidized LDLs are also present in saliva fluid (De Giuseppe et al 2015), and recently, Bright et al (2018) reported that malondialdehyde acetaldehyde (MAA) adducts are increased in gingivitis and periodontitis lesions.…”