A To-Do List at Diagnosis of Systemic Sclerosis with Positive Anti-RNA Polymerase III Antibodies
Bibliographic record
Abstract
The presence of circulating antinuclear antibodies (ANA) is one of the distinctive features of systemic sclerosis (SSc), or scleroderma. A variety of SSc-related ANA, including anticentromere antibody (ACA), antitopoisomerase I antibody (anti–topo I), and anti-RNA polymerase (RNAP) III antibody, have been well characterized and are used in our daily clinical practice. They are specific to SSc and are associated with unique sets of disease manifestations. Because of their mutual exclusiveness, SSc-related ANA are widely used for diagnosis, designation of clinical subsets, and prediction of future organ involvement and prognosis1. Serum autoantibodies reactive with multiple RNAP specificities, including RNAP III, were first identified by our group in 1993 using an immunoprecipitation assay2. We reported anti-RNAP III antibody as a biomarker that is highly specific to SSc and is associated with diffuse cutaneous SSc (dcSSc) and scleroderma renal crisis (SRC). After our initial report, these clinical correlations were confirmed by several independent studies, but anti-RNAP III antibody measurement was not used in clinical practice because an immunoprecipitation assay, which requires complicated procedures with a radioisotope and cultured human cell line, was the only method for detection. Because eukaryotic RNAP III consists of at least 13 subunits, identification of antigenic epitope(s) recognized by all anti-RNAP III–positive sera is necessary for development of convenient immunoassays. To overcome this limitation, we conducted a series of experiments using individual subunits and their recombinant fragments, and successfully identified the central portion of the largest subunit RPC155/POLR3A as the major antigenic site universally recognized by anti-RNAP III–positive SSc sera3,4. Use of the recombinant antigenic fragment enabled us to establish a sensitive and specific immunoassay system4. Currently, commercial immunoassay kits using this system (MBL, INOVA, and Phadia) are available as in vitro diagnostics in many countries. This evolution has … Address correspondence to Prof. M. Kuwana; E-mail: kuwanam{at}nms.ac.jp
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.019 | 0.004 |
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".