BACKGROUND: RA is characterized by chronic inflammation of the synovium caused by the interaction of genes, environment and immunity. Smoking leads to guanylation of lung tissue, which in those carrying genetic susceptibility genes will likely produce an anti-citrulline immune response and persistent inflammation of the joints, typical of the genetic, environmental and immune interactions leading to disease. We herein propose other predisposing factors for RA, such as periodontitis caused by infections such as Porphyromonas gingivalis that may undergo alterations similar to those caused by smoking, thereby triggering RA. OBJECTIVE: To investigate the presence of guanylated proteins and PAD-2 enzymes in periodontal tissue. METHODS: Gingival tissues from 15 patients with gingivitis and 15 healthy controls were biopsied, fixed with formalin, and paraffin-embedded sections were taken. Inflammation levels, guanosine protein and PAD-2 expression were analyzed by immunohistochemistry, and serial sections of tissue were analyzed by triple-blind, semi-quantitative, four-level classification criteria. The Mann-Wyeji test and Fisher’s exact test were used to analyze the differences in guanylated protein expression and guanylated protein positivity between the two groups. RESULTS: Periodontal tissue inflammation scores were higher in patients with gingivitis than in the healthy group. The detection rate of guanylated proteins in subepithelial cells was higher in patients with periodontitis (80%, 12/15) than in healthy controls (37%, 5/14), as was the rate of guanylated protein positivity in subepithelial connective tissue (80%, 12/15) than in healthy controls (43%, 6/14), but there were no differences between epithelial layers. PAD2 was expressed in both epithelial and subepithelial layers, but there were no differences between the two groups. CONCLUSION: Chronic gingivitis may lead to guanylation of the protein. Similar to smoking, chronic inflammation due to bacterial infection may be involved in the anti-citrulline immune response in rheumatoid susceptible individuals.