The P. gingivalis Autocitrullinome Is Not a Target for ACPA in Early Rheumatoid Arthritis

Rheumatoid arthritis (RA), a chronic inflammatory disease affecting primarily the joints, is frequently characterized by the presence of autoimmune anticitrullinated protein antibodies (ACPA) during preclinical stages of disease and accumulation of hypercitrullinated proteins in arthritic joints. A...

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Vydáno v:Journal of dental research Ročník 99; číslo 4; s. 456
Hlavní autoři: Muñoz-Atienza, E, Flak, M B, Sirr, J, Paramonov, N A, Aduse-Opoku, J, Pitzalis, C, Curtis, M A
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.04.2020
Témata:
Animals
Arthritis, Rheumatoid
Humans
Mice
Periodontitis
Porphyromonas gingivalis - genetics
Protein-Arginine Deiminases
RNA, Ribosomal, 16S
microbiota
P. gingivalis peptidylarginine deiminase
autoimmune responses
immunocrossreactivity
chronic inflammation
periodontitis
ISSN:1544-0591, 1544-0591
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Shrnutí:Rheumatoid arthritis (RA), a chronic inflammatory disease affecting primarily the joints, is frequently characterized by the presence of autoimmune anticitrullinated protein antibodies (ACPA) during preclinical stages of disease and accumulation of hypercitrullinated proteins in arthritic joints. A strong association has been reported between RA and periodontal disease, and , a known driver of periodontitis, has been proposed as the microbial link underlying this association. We recently demonstrated -mediated gut barrier breakdown and exacerbation of joint inflammation during inflammatory arthritis. In the present study, we investigated another potential role for in RA etiopathogenesis, based on the generation of ACPA through the activity of a unique peptidylarginine deiminase (PPAD) produced by this bacterium, which is capable of protein citrullination. Using a novel W50 PPAD mutant strain, incapable of protein citrullination, and serum from disease-modifying antirheumatic drug-naïve early arthritis patients, we assessed whether autocitrullinated proteins in the proteome serve as cross-activation targets in the initiation of ACPA production. We found no evidence for patient antibody activity specific to autocitrullinated proteins. Moreover, deletion of PPAD did not prevent -mediated intestinal barrier breakdown and exacerbation of disease during inflammatory arthritis in a murine model. Together, these findings suggest that the enzymatic activity of PPAD is not a major virulence mechanism during early stages of inflammatory arthritis.
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ISSN:1544-0591
1544-0591
DOI:10.1177/0022034519898144