Expression of peptidylarginine deiminase-2 and -4, citrullinated proteins and anti-citrullinated protein antibodies in human gingiva.

The presence of citrullinated proteins, and peptidylarginine deiminase types -2 (PAD-2) and -4 (PAD-4) in periodontal tissues, determine the presence of anti-cyclic citrullinated protein antibodies (anti-CCP) in gingival crevicular fluid (GCF) and compare the expression of these proteins between inflamed and non-inflamed sites. Tissue sections were stained using antibodies against citrullinated proteins, PAD-2 and PAD-4. RT-PCR was performed to investigate PAD-2 and PAD-4 mRNA in inflamed and non-inflamed gingival tissues. Anti-CCP antibodies in gingival crevicular fluid were detected by ELISA. Citrullinated proteins, PAD-2 and PAD-4 were detected in gingiva. There was a correlation between inflammation and expression of these proteins. mRNAs for PAD-2 and PAD-4 were detected in both inflamed and non-inflamed gingival tissues. Antibodies to CCP were found mostly in the GCF of individuals with periodontitis. PAD-2 and PAD-4 (protein and mRNA) as well as citrullinated proteins are present in inflamed gingiva, and anti-CCP antibodies can be detected in the GCF of some patients. Tissue expression of citrullinated proteins and PAD increased with the severity of inflammation. The presence of anti-CCP antibodies in GCF was almost exclusive to a subset of patients with periodontitis. Increased expression of these proteins in inflamed gingiva lends support to the notion that periodontal inflammation contributes to the inflammatory burden in a similar way to rheumatoid arthritis.