Activities of Porphyromonas gingivalis peptidylarginine-deiminase in periodontitis and rheumatoid arthritis

Several studies focus on a relationship between periodontitis (PA) and rheumatoid arthritis (RA). Citrullination of proteins and peptides by human peptidylarginine-deiminases (PAD) followed by generation of antibodies is an important factor in RA. Recently a PAD has been purified from Porphyromonas gingivalis (PPAD) being unique in bacteria. The aim of this case-control study was to determine activities of PAD and PPAD in periodontium and serum antibody levels against citrullinated epitopes of PPAD in RA patients.

Method:

Gingival crevicular washes of 52 RA patients (48 with PA (RA-PA) and 4 without (RA-NoPA)) and 44 individuals without RA (NoRA, 28 with PA (NoRA-PA) and 16 without PA (NoRA-NoPA)) have been evaluated for activities of PAD and PPAD and for presence of Porphyromonas gingivalis. Serum has been analyzed for antibodies against citrullinated epitopes of PPAD. 

Result:

PAD activity has been detected in 25 (48%) of RA patients (24 RA-PA) and in 24 (55%) of NoRA (19 NoRA-PA). PPAD activity has been measured in 30 (58%) of RA-patients (29 RA-PA) and in 21 (50%) of No-RA-patients (19 NoRA-PA). Enzyme activities were significantly higher in NoRA-PA compared with NoRA-NoPA (p=0.022; p=0.004). PPAD activity correlated neither with PAD activity nor with counts of P. gingivalis.  In contrast PPAD activity has also been detected in 16 out of 38 P. gingivalis negative samples. PPAD positive but P. gingivalis negative samples showed high antibody levels against citrullinated epitopes of PPAD.

Conclusion:

Peptidylarginine-deiminases are active within the periodontium and can citrullinate proteins and peptides. P. gingivalis seems to be able to release PPAD acting in sites not colonized by the species. The citrullination by human PAD and PPAD may generate antibodies after breaking immunotolerance in susceptible individuals.