Autoimmunity as a principal pathogenic factor in the refined model of neuropsychiatric lupus
Bibliographic record
Abstract
Abstract Objectives: Over the past decades, the MRL mouse model had shown significant validity in elucidating the pathogenesis of neuropsychiatric lupus erythematosus (NP SLE). However, the possibility that the inherited Fas receptor deficiency (and not autoimmunity) accounts for central nervous system (CNS) damage in the original stock 485 of MRL/MpJ‐Faslpr mice could not be rejected. The aim of the present study was to examine the consequences of autoimmune disease on behavior and brain morphology, while controlling for the genetic deficiency with a new, less symptomatic 6825 stock. Methods: Spleen mass, serum autoantibody and cytokine levels, immunoglobulins in cerebrospinal fluid (CSF), and brain planimetry were used to assess disease severity and CNS involvement in 5‐month‐old mice from stocks 6825 and 485. Their behavioral profiles were compared in a standard battery of tasks. The 2D‐DIGE and mass spectrometry examined brain antigens targeted by autoantibodies from serum and CSF. Results: The 6825 mice had smaller spleens, lower antibody and cytokine levels, and less IgG in the CSF. They were more active and showed better performance in tasks reflective of anxiety and motivated behavior. Signs of brain pathology were less profound and their CSF autoantibodies showed reduced affinity for brain antigens, largely characterized as highly‐conserved cytoskeletal proteins. Conclusions: The constellation of differences between the two MRL/MpJ‐Faslpr stocks confirms that the lpr mutation per se does not account for the brain pathology and altered behavior in the 485 stock. Together with significant correlations between immunological and behavioral measures, this observation suggests that soluble immune factors play a key role in pathogenesis of NP SLE. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2010.00014.x, September 2010)
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".