Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis?
Peptidylarginine deiminases (PADs) convert arginine within a peptide (peptidylarginine) into peptidylcitrulline. Citrullination by human PADs is important in normal physiology and inflammation. Porphyromonas gingivalis, a major pathogen in periodontitis, is the only prokaryote described to possess PAD. P. gingivalis infection may generate citrullinated peptides, which trigger anti-citrullinated peptide antibodies. In susceptible individuals, host protein citrullination by human PADs in the joint probably perpetuates antibody formation, paving the way for the development of chronic arthritis. Blockades of bacterial and human PADs may act as powerful novel therapies by inhibiting the generation of the antigens that trigger and sustain autoimmunity in rheumatoid arthritis.
Mangat
Pamela
P
The Kennedy Institute of Rheumatology Division, Imperial College, 65 Aspenlea Road, London, W6 8LH, UK.
Wegner
Natalia
N
Venables
Patrick J
PJ
Potempa
Jan
J
D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000503:physiopathology*; D015551:Autoimmunity / Q000502:physiology*; D006801:Humans; D006867:Hydrolases / Q000502:physiology*; D008969:Molecular Sequence Data; D010518:Periodontitis / Q000150:complications; D016966:Porphyromonas gingivalis / Q000502:physiology; D000076342:Protein-Arginine Deiminases; D012307:Risk Factors
D006867:Hydrolases; D000076342:Protein-Arginine Deiminases