Association of Porphyromonas gingivalis peptidylarginine deiminase with CitH3, LL‐37, and ACPA in periodontitis and rheumatoid arthritis

BACKGROUND: Porphyromonas gingivalis peptidyl-arginine deiminase (PPAD) enzyme has been implicated in rheumatoid arthritis (RA) pathogenesis through protein citrullination and its potential contribution to neutrophil-associated inflammatory responses and anti-citrullinated protein antibody (ACPA) autoimmunity. However, its role in early stages of RA remains unclear. This study investigated the association of PPAD with citrullinated histone H3 (CitH3), cathelicidin (LL-37), and ACPA in preclinical RA (preRA), early RA (eRA), and established RA (RA), with and without periodontitis (PD). METHODS: 108 participants were categorized into preRA, eRA, RA, and nonRA controls with and without PD. Periodontal and rheumatological parameters were assessed. ppad gene expression was quantified in subgingival plaque samples, and salivary and serum levels of CitH3, LL-37 and ACPA were measured. Data were analyzed with SPSS version 26. RESULTS: ppad expression was elevated in all PD groups, irrespective of RA status. Among PD groups, ppad correlated with salivary CitH3 only in eRA-PD (r = 0.628) and with serum ACPA only in RA-PD (r = 0.503), while no significant associations were detected between ppad and LL-37. CitH3 was not associated with serum ACPA in any PD group. As secondary findings, salivary CitH3 correlated with gingival bleeding index (GBI) in eRA-PD (r = 0.628) and RA-PD (r = 0.608) while serum LL-37 correlated with serum ACPA in eRA-PD (r = 0.767), CONCLUSION: Elevated ppad expression was primarily associated with PD rather than RA status. PPADs association with salivary CitH3 in eRA-PD suggests its strong role in periodontal inflammation during early phases of RA but disproves a mechanistic link between PPAD to NETs and RA.