The Antinuclear Antibody Test in the Diagnosis of Antisynthetase Syndrome and Other Autoimmune Myopathies
Bibliographic record
Abstract
Autoantibodies directed to intracellular macromolecules are a characteristic feature of antinuclear antibody (ANA)-associated rheumatic diseases (AARD) such as systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, Sjögren syndrome, and autoimmune inflammatory myopathies (AIM). Some of these autoantibodies are highly specific for the individual AARD and hence are termed disease-specific antibodies, and some are included in the classification and/or diagnostic criteria for these diseases1. In this context, the report by Aggarwal, et al in The Journal 2 is timely and provides insight into the value of screening for anticytoplasmic antibodies (anti-CytAb) as an adjunct to the diagnosis of the antisynthetase syndrome, a subset of AIM3. In their retrospective analysis of 202 patients with antisynthetase syndrome, the anti-CytAb test performed better than the conventional ANA indirect immunofluorescence (IIF) test in identifying antisynthetase syndrome as evidenced by higher sensitivity (72% vs 50%) and specificity (89% vs 6%). Consequently, they indicate that a negative ANA test does not rule out the diagnosis of antisynthetase syndrome or AIM. That a negative ANA does not indicate autoantibody negativity in antisynthetase syndrome or AIM is an important message that may be misunderstood by clinicians. Despite remarkable efforts to standardize ANA nomenclature by the International Consensus on ANA Pattern (ICAP) committee4,5, there is considerable confusion about the term ANA . The efforts of the ICAP were recognized by Aggarwal, et al , but they, as well as some diagnostic laboratories and clinicians, continue to interpret and understand the definition of ANA in a strict sense, meaning only autoantibodies that react with nuclear targets are properly regarded as ANA. The spectrum of autoantibody targets in the nucleus is wide and includes components of the nuclear envelope, nuclear pore complex, nuclear matrix, nucleoplasm, chromatin and chromosomes, nucleolus, and promyelocyte leukemia/coiled bodies … Address correspondence to Dr. M.J. Fritzler, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada. E-mail: fritzler{at}ucalgary.ca
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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 | 0.007 | 0.015 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".