PtpA protein from Mycobacterium avium subsp. paratuberculosis as a potential marker of rheumatoid arthritis in humans

by Jorge Hernández-Bello, Horacio Bach, Sergio Cerpa-Cruz, Gabriela Athziri Sánchez-Zuno, Rodolfo Hernández-Gutiérrez, Ferdinando Nicoletti, Andrea Saraceno, José Muñoz-Valle

Studies have noted the connection between Mycobacterium avium subspecies paratuberculosis (MAP) and autoimmunity. MAP is an intracellular pathogen that infects and multiplies in macrophages. To overcome the hostile environment elicited by the macrophage, MAP secretes a battery of virulence factors to neutralize the toxic effects of the macrophage. One of the virulence factors is the Protein Tyrosine Phosphatase A (PtpA), a protein secreted by MAP that interferes in the phago-lysosome fusion, rendering the pathogen unnoticed in the cytoplasm of the macrophage. This study aimed to assess the presence of PtpA antibodies in the sera of Mexican individuals with rheumatoid arthritis (RA) and investigate its possible use as a biomarker for disease activity. We compared RA patients (n = 100) to control subjects (CS) (n = 100) by assessing specific immune responses to PtpA (the antigen) by an indirect ELISA method. Results showed a significant difference in PtpA levels between RA and CS, with RA patients having a median OD of 0.4645 compared to 0.1372 in CS. Antibodies against PtpA were present in 95% of RA patients and 16% of CS (AUC = 0.9163, p = 0.0001). Male control subjects showed higher PtpA reactivity than female CS. The Disease Activity Score (DAS-28) analysis showed that individuals with moderate to high disease activity had lower levels of PtpA reactivity. The results suggest a potential connection between RA and MAP infection.