Overexpression of the autoantigen hnRNP-A2 (RA33), the tumour suppressor p53 and activated MAP-Kinase p38 in inflamed synovial tissue
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Overexpression of the nuclear autoantigen hnRNP-A2 (RA33) has recently been observed in synovial tissue of RA patients and TNF transgenic mice. To further investigate this issue expression of hnRNP-A2 was compared with that of two other hnRNP proteins, the closely related hnRNP-A1 (a rare autoantigen in RA) and the structurally different hnRNP-C (which is not an autoantigen). In addition, expression of the tumour suppressor p53 and the MAP-kinase p38 was studied. Synovial tissue of patiens with RA or osteoarthitis and specimen from patients with early arthritis of <1 year duration were analyzed by immunohistochemistry HnRNP-A2 was highly overexpressed in RA synovial tissue as compared to tissue of osteoarthritis patients, and most abundantly found in CD68-positive cells of the lining layer. The antigen was not only localized in the nucleus but also in the cytoplasm confirming previous observations. Nuclear overexpression was also observed for hnRNP-C, whereas expression of hnRNP-A1 appeared normal. Remarkably, in the majority of hnRNP-A2 expressing cells also the p53 tumor suppressor was overexpressed and aberrantly localized in the cytoplasm. Furthermore, the MAP-kinase p38 was acitvated in these cells as revealed by a monoclonal antibody specifically recognizing the phosphorylated (activated) form of this kinase. This indicated that cells over-expressing hnRNP-A2 and p53 had been activated by proinflammatory cytokines such as TNF or IL-1. A comparable result was obtained with tissue from patients with early arthritis, irrespectively of their diagnosis (RA or reactive arthritis). So far, the conditions that lead to aberrant expression of these proteins have not been clearly defined since even prolonged exposure of macrophages or synovial fibroblasts to TNF or IL-1 did not cause any changes in hnRNP-A2 expression or induce its cytoplasmic accumulation. This was only achieved by treatment with the RNA polymeraseII inhibitor actinomycin D which subsequently led to apoptosis and accumulation of hnRNP-A2 in apoptotic bodies. The state of chronic inflammation in the rheumatoid synovium seems to cause aberrant expression and/or modification of (some) proteins which may lead to loss of tolerance and induction of patholocigal autoimmune reactions in genetically susceptible individuals.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it