PtpA protein from Mycobacterium avium subsp. paratuberculosis as a potential marker of rheumatoid arthritis in humans
Jorge Hernández-Bello1, Horacio Bach2, Sergio Cerpa-Cruz3
1Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud Universidad de Guadalajara, Guadalajara, Mexico.
Abstract:
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.
Insights
This study found higher levels of antibodies against Mycobacterium avium subspecies paratuberculosis (MAP) Protein Tyrosine Phosphatase A (PtpA) in Mexican rheumatoid arthritis (RA) patients. This suggests a potential link between MAP infection and RA development.
Area of Science:
- Immunology
- Microbiology
- Rheumatology
Background:
- Mycobacterium avium subspecies paratuberculosis (MAP) is an intracellular pathogen linked to autoimmune diseases.
- MAP secretes virulence factors, such as Protein Tyrosine Phosphatase A (PtpA), to evade host immune responses within macrophages.
- PtpA interferes with phagolysosome fusion, allowing MAP to survive intracellularly.
Purpose of the Study:
- To investigate the presence of PtpA antibodies in Mexican individuals with rheumatoid arthritis (RA).
- To explore the potential of PtpA as a biomarker for RA disease activity.
Main Methods:
- An indirect ELISA method was used to assess specific immune responses to PtpA.
- Sera from RA patients (n=100) and control subjects (CS, n=100) were analyzed.
- PtpA antibody levels were correlated with disease activity using the DAS-28 score.
Main Results:
- Antibodies against PtpA were detected in 95% of RA patients compared to 16% of CS (p=0.0001).
- RA patients showed significantly higher PtpA antibody levels (median OD 0.4645) than CS (median OD 0.1372).
- Individuals with moderate to high RA disease activity exhibited lower PtpA antibody levels.
Conclusions:
- The findings suggest a potential association between MAP infection and rheumatoid arthritis in the studied population.
- PtpA antibodies may serve as a potential biomarker for RA, although further research is needed.
- The inverse correlation between PtpA levels and disease activity warrants further investigation.
