FMF Is Associated With a Wide Spectrum of MHC Class I- and Allied SpA Disorders but Not With Classical MHC Class II-Associated Autoimmune Disease: Insights From a Large Cohort Study
Bibliographic record
Abstract
Objectives: To test the hypothesis that familial Meditteranean fever (FMF) associated autoinflammation may exaggerate the tendency towards adaptive immunopathology or spondyloarthritis (SpA)-associated disorders including MHC class-I associated disorders but not classical MHC class II-associated disorders that exhibit transplacental autoimmunity including myasthenia gravis and pemphigus. Methods: 7,747 FMF patients and 10,080 age- and sex-matched controls in the Clalit-Health-Services medical database were identified and compared in terms of prevalence of SpA-associated disorders and also evaluated 4 classical and strong MHC class-II associated disorders, namely pemphigus vulgaris, myasthenia gravis, sarcoidosis and pernicious anaemia, to ascertain whether such associations with SpA-spectrum disease were specific or merely reflected the non-specific consequences of innate immune system activation on driving divergent types of immunity. Results: FMF showed a strong association with MHC class I related diseases: OR 28.58 ([95%CI 6.93-117.87], p<0.0001) for Behçet’s disease, OR of 10.33 ([95%CI 4.09-26.09], p<0.0001) for AS, and OR 1.67 ([95%CI 1.19-2.33], p=0.0029) for psoriasis. For weakly MHC class I linked diseases, an OR of 3.76 ([95%CI 2.48-5.69], p<0.0001) for Crohn’s disease and OR of 2.64 ([95%CI 1.52-4.56], p=0.0005) for ulcerative colitis were found. No association was found between FMF and the four MHC class II-associated autoimmune disorders. Conclusion: FMF patients are associated with increased risk of SpA-related disease diagnosis including MHC-I-opathies but not MHC-II associated autoimmune diseases suggesting that tissue-specific dysregulation of innate immunity share between FMF and SpA spectrum disorders may drive adaptive immune MHC class I-associated conditions.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".