Treatment of Crohn's disease patients with infliximab is detrimental for the survival of Mycobacterium avium ssp. paratuberculosis within macrophages and shows a remarkable decrease in the immunogenicity of mycobacterial proteins
Bibliographic record
Abstract
Dear Sir, The association between Mycobacterium avium ssp. paratuberculosis (MAP) and Crohn's disease (CD) although debatable, is supported by several studies 1 which have reported the detection or isolation of MAP from human tissues 2 including serum, 3 body fluids (breast milk), 4 and high levels of TNF-α was found secreted by the gut mucosa in MAP-associated CD patients. 5 Infliximab is a monoclonal antibody that specifically inhibits TNF-α and is used as a current therapy for CD. Recently, Nakase et al. 6 demonstrated that THP-1 cells infected with MAP induced the production of a higher amount of TNF-α when compared to macrophages infected with either Mycobacterium avium or Mycobacterium smegmatis , suggesting that MAP is directly involved in the upregulation of this cytokine. Previously, we have reported that MAP is able to infect, reside, and multiply intracellularly in human macrophages, 7 , 8 suggesting that the pathogen is able to subvert the host's immune response to avoid its own demise even at the earliest stage of the infection. Moreover, we have reported that CD patients, 8 but not healthy controls, have a significantly higher level of antibodies against two MAP proteins, a Protein tyrosine phosphatase (PtpA), and a Protein kinase (PknG). Both proteins are part of the signal transduction system of the bacterium, have been shown to be secreted within the host, and are essential for the intracellular survival and the establishment of a successful infection of the MAP's close relative Mycobacterium tuberculosis . 9 , 10 Therefore, to persist within the host, both proteins have to be secreted in a regular manner by the pathogen, in order to manipulate the immunological response elicited by macrophages. Recently, we have shown that CD patients possess a higher titer of antibodies against PtpA and PknG when compared to healthy controls, 8 and we suggested that both proteins can be used to determine the status of MAP in CD patients.
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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 | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".