Arg‐gingipain, myeloperoxidase, and anti‐CarP across the rheumatoid arthritis spectrum

Abstract Background The association between periodontitis (PD) and rheumatoid arthritis (RA) has been linked to autoantibodies. In recent years, Arg‐gingipain (Rgp) triggered myeloperoxidase (MPO) release, which mediates protein carbamylation to form anti‐carbamylated proteins (anti‐CarP), perpetuating RA progression has gained interest. This study assessed the association between Rgp with MPO and anti‐CarP in pre‐clinical RA (preRA), early RA (eRA), and established RA (RA) participants with PD. Methods A total of 108 participants were categorized into preRA, eRA, RA, and nonRA controls with and without PD. Periodontal and rheumatological parameters were assessed. Rgp‐B gene expression from subgingival plaque and MPO and anti‐CarP in saliva and serum were assessed. Data were analyzed with SPSS Version 26. Results Rgp‐B gene expressions were similar across PD groups. In eRA‐PD, serum and saliva MPO and saliva anti‐CarP levels were highest; strong correlations were present between rgp‐B with clinical attachment loss (CAL) ( r = 0.783), salivary MPO with visible plaque index (VPI) ( r = 0.667), and gingival bleeding index (GBI) ( r = 0.767), and salivary anti‐CarP with CAL ( r = 0.667) and GBI ( r = 0.850). Strong positive correlations were detected between salivary MPO and anti‐CarP in preRA‐PD ( r = 0.903), eRA‐PD ( r = 0.783), RA‐PD ( r = 0.726), and nonRA‐PD ( r = 0.470). Conclusion Rgp‐B gene expression was associated with PD status. Periodontal inflammation, particularly in early RA, was linked to elevated MPO and anti‐CarP levels, suggesting that local inflammation may amplify immune responses via MPO‐mediated carbamylation. These associations highlight the clinical relevance of periodontal assessment and management in RA patients and at‐risk individuals. Plain Language Summary Periodontitis (PD) and rheumatoid arthritis (RA) are chronic inflammatory diseases that may be linked through immune system activity. Studies suggest RA can begin developing before symptoms appear (preRA), with early immune changes occurring in the body. One possible trigger is the occurrence of myeloperoxidase (MPO)‐mediated carbamylation in the inflamed periodontium during the earliest phases of RA, which may precede the occurrence of autoantibodies, particularly anti‐carbamylated proteins (anti‐CarP). To date, these changes due to PD at different stages of RA have not been studied. This study investigated whether the Porphyromonas gingivalis enzyme, Arg‐gingipain (Rgp) is linked to MPO and anti‐CarP levels in individuals at different stages of RA. A total of 108 participants were recruited for this study, including preRA, early RA (eRA), established RA (RA), and healthy individuals (nonRA), with and without PD. Periodontal and rheumatological assessments were conducted. Rgp‐B gene expressions were analyzed in subgingival plaque, and MPO and anti‐CarP levels were measured in saliva and serum samples. Findings revealed that eRA participants with PD had the highest MPO and anti‐CarP levels, which strongly correlated with periodontal inflammation. Additionally, MPO and anti‐CarP were strongly correlated in all PD groups. These findings suggest that periodontal inflammation, especially in early RA, may contribute to immune responses involved in RA progression.