Expansion of Alternative Autoantibodies Does Not Follow the Evolution of Anti–Citrullinated Protein Antibodies in Preclinical Rheumatoid Arthritis: An Analysis in At‐Risk First Degree Relatives
Bibliographic record
Abstract
OBJECTIVE: Co-occurrence of autoantibodies specific for ≥1 autoimmune disease is widely prevalent in rheumatoid arthritis (RA) patients. To understand the prevalence of polyautoimmunity in preclinical RA, we performed a comprehensive autoantibody assessment in a First Nations cohort of at-risk first-degree relatives (FDR) of RA patients, a subset of whom subsequently developed RA (progressors). METHODS: Venous blood was collected from all study participants (n = 50 RA patients and 64 FDR) at scheduled visits, and serum was stored at -20°C. High-sensitivity C-reactive protein level, anti-citrullinated protein antibody (ACPA) status, and autoantibody status were determined using commercially available enzyme-linked immunosorbent assay kits. Rheumatoid factor (RF) was detected by nephelometry. Antinuclear autoantibodies (ANA) were identified using Hep-2 indirect immunofluorescence assay (IFA) and classified according to international consensus nomenclature as various anti-cell (AC) patterns. RESULTS: Of our study cohort, 78.9% had positive ANA reactivity (≥1:80), which was either a homogenous, fine-speckled (AC-1 and AC-4) or mixed IFA pattern. Importantly, the AC-4 and mixed ANA patterns were also observed in progressors at the time of disease onset. While all of the RA patients showed a high prevalence of arthritis-associated autoantibodies, they also had a high prevalence of extractable nuclear antigen-positive autoantibodies to other autoantigens. In FDR, we did not observe any increase in serum autoreactivity to nonarthritis autoantigens, either cross-sectionally or in samples collected longitudinally from progressors prior to RA onset. CONCLUSION: While alternative autoimmunity and ANA positivity are widely prevalent in First Nations populations, including asymptomatic, seronegative FDR, expansion of alternative autoimmunity does not occur in parallel with ACPA expansion in FDR and is restricted to patients with established RA.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 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) | 0.002 | 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".