PtpA and PknG Proteins Secreted by Mycobacterium avium subsp. paratuberculosis are Recognized by Sera from Patients with Rheumatoid Arthritis: A Case–Control Study
Bibliographic record
Abstract
Marco Bo,1 Gian Luca Erre,2 Horacio Bach,3 Yael N Slavin,3 Piera Angela Manchia,4 Giuseppe Passiu,2 Leonardo A Sechi1 1Department of Biomedical Sciences, Section of Microbiology and Virology, University of Sassari, Sassari 07100, Italy; 2Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria di Sassari, UOC di Reumatologia, Sassari 07100, Italy; 3Division of Infectious Diseases, Faculty of Medicine, The University of British Columbia, Vancouver, BC V6H 3Z6, Canada; 4Centro Trasfusionale, AOU Sassari, Sassari, ItalyCorrespondence: Leonardo A SechiDepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43 B, Sassari 07100, ItalyTel +39 079228462Email sechila@uniss.itPurpose: 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.Keywords: Mycobacterium avium subsp. paratuberculosis, PtpA, PknG, virulence factors, rheumatoid arthritis, immune response
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".