The Molecular Analysis of Rheumatoid Arthritis-related Gene LRG1 in Periodontitis

Objectives: Periodontitis is caused by the interaction between host immune response and bacterial challenge. Rheumatoid arthritis (RA) is also inflammatory disease caused by the increase of autoantigen against citrullinated protein (CP). The correlation between periodontitis and RA is the acceptable fact via the elevated level of CP produced by Porphyromonas gingivalis (Pg). Recently, biologics (neutralization antibodies for IL-6 and TNF-alpha) was approved to treat RA. However, the evaluation of inflammatory response by CRP, which is regulated by inflammatory cytokine, is sometimes difficult for patient in the circumstance of using biologics. Therefore, in this study, the new target of leucine-rich alpha-2-glycoprotein 1 (LRG1), which is not affected by inflammatory cytokine, was focused on.
Methods: To detect the production of LRG1 in RA patients, serum was collected by the approved experimental protocol of the Ethical Committee of Hiroshima University (approved No. 781). LRG1 in patients’ sera was detected by Western blotting. The level of anti-CP antibody was measured by ELISA. The serum LRG1 in RA mice model previously established was also determined with/without Pg infection. The mRNA expression of LRG1 in primary cultured human gingival fibroblast (HGF) was determined by real time PCR in the presence or absence of Pg. The biological effect of LRG1 in HGF was determined by real-time PCR with/without LRG1.
Results: The LRG1 was detected in patients’ sera and showed the correlation with the level of anti-CP antibody. The production of LRG1 in mice RA model was induced by the additional infection of Pg. The mRNA expression of LRG1 was induced by the Pg stimulation in HGF. The mRNA expression of IL-8 was strongly induced by the addition of LRG1 in HGF.
Conclusions: These results showed that LRG1 might be a new target for diagnosis and treatment of periodontitis and RA.