Porphyromonas gingivalis with collagen immunization induces ACPA-positive rheumatoid arthritis in C3H mice

Abstract

The pathogenic anti-citrullinated protein antibodies (ACPA) are thought to play a vital role in the initiation and immune maintenance of rheumatoid arthritis (RA). However, it is noteworthy that ACPA is not a salient characteristic of any conventional RA animal model. Porphyromonas gingivalis (Pg) is the first microorganism identified to induce citrullination and a target of autoantibodies in early rheumatoid arthritis (RA). Thus, we employed C3H mice with specific MHC types and combined Pg infection with collagen immunity to develop an animal model of ACPA-positive RA. The resulting model exhibited citrullination characteristics, as well as pathological and immune cell changes. 1) Mice showed a significant increase in ACPA levels, and various organs and tissues exhibited elevated levels of citrullinated protein. 2) The mice experienced heightened pain, inflammation, and bone destruction. 3) The spleen and lymph nodes of the mice showed a significant increase in the proportion of Tfh-GCB cell subpopulations responsible for regulating autoantibody production. In conclusion, the C3H mouse model of Pg infection with collagen immunity demonstrated significant alterations in ACPA levels, citrullinated protein expression, and immune cell subpopulations, which could be a crucial factor leading to increased pain, inflammation, and bone destruction.

Keywords: Anti-citrullinated protein antibodies; C3H mice; Collagen-induced arthritis; Porphyromonas gingivalis; Rheumatoid arthritis.