Abstract
Purpose
Rheumatoid arthritis (RA) can result from complex interactions between the affected person’s genetic background and environment. Viral and bacterial infections may play a pathogenetic role in RA through different mechanisms of action. We aimed to evaluate the presence of antibodies (Abs) directed against two proteins of Mycobacterium avium subsp. paratuberculosis (MAP) in sera of RA subjects, which are crucial for the survival of the pathogen within macrophages. Moreover, we analyzed the correlation of immune response to both proteins with the following homologous peptides: BOLF1305–320, MAP_402718–32 and IRF5424–434 to understand how the synergic role of Epstein–Barr virus (EBV) and MAP infection in genetically predisposed subjects may lead to a possible deregulation of interferon regulatory factor 5 (IRF5).
Materials and methods
The presence of Abs against protein tyrosine phosphatase A (PtpA) and protein kinase G (PknG) in sera from Sardinian RA patients (n=84) and healthy volunteers (HCs, n=79) was tested by indirect ELISA.
Results
RA sera showed a remarkably high frequency of reactivity against PtpA in comparison to HCs (48.8% vs 7.6%; p<0.001) and lower but statistically significant responses towards PknG (27.4% vs 10.1%; p=0.0054). We found a significant linear correlation between the number of swollen joints and the concentrations of antibodies against PtpA (p=0.018). Furthermore, a significant bivariate correlation between PtpA and MAP MAP_402718–32 peptide has been found, suggesting that MAP infection may induce a secondary immune response through cross-reaction with IRF5 (R2=0.5).
Conclusion
PtpA and PknG are strongly recognized in RA which supports the hypothesis that MAP infection may be involved in the pathogenesis of RA.
Acknowledgments
PORFSE Sardinia. “Finanziamento straordinario una tantum per la ricerca” 2019, Università di Sassari to Prof Sechi and Prof Passiu. Prof Bach contributed for the publishing fee with personal grant.
Author Contributions
All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.