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 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".