AI-08 B cell phenotypic changes in anti-nuclear antibody positive individuals prior to the onset of systemic autoimmune rheumatic disease
Bibliographic record
Abstract
Background Patients with systemic autoimmune rheumatic diseases (SARD) often have a prolonged pre-clinical phase during which they are anti-nuclear antibody (ANA)+ but lack clinical symptoms. Here we sought to determine whether ANA+ individuals who lack sufficient symptoms for a SARD diagnosis share the B cell phenotypic changes seen in SARD. Materials and methods Healthy controls (HC) and ANA+ individuals who: 1) lacked clinical symptoms of SARD (ANS); 2) had at least one clinical symptom of SARD (UCTD); or 3) had recently diagnosed steroid and immunosuppressive naïve SARD (SLE, SS, SSc, MCTD, DM) were recruited. PBMCs were stained with various combinations of fluorescently labelled antibodies and analysed by flow cytometry. Anti-nuclear antibodies were measured through the hospital laboratory. Whole blood IFN signature and BAFF RNA levels were measured by NanoString. Results B cell phenotypes were examined for 32 HC, 38 ANS, 28 UCTD, and 59 early SARD patients. Patients with early SARD had a number of changes in their naïve and memory B cell subsets including: increased proportions of mature naïve (SSc) and T1T2 cells (SLE and SS), and decreased proportions of switched memory cells (all SARD). Similar decreases in the proportion of switched memory B cells were seen in ANS and UCTD patients, and as seen for the SARD patients, these cells were activated with elevated levels of CD86 as compared to HC. Significantly increased activation of the CD27-IgD- memory compartment was also seen in ANS, UCTD, SLE and SjD patients. Although significantly increased proportions of plasmablasts and/or CD138+ plasma cells were seen in early SARD patients, these were not seen in ANS and UCTD patients. Nevertheless, in pre-SARD individuals (ANS + UCTD) there was a significant positive correlation between the size of these cell subsets and ANA titer as well as the number of different anti-nuclear antibody specificities. As observed for early SARD patients, there was a trend to increased BAFF levels as compared to HC in pre-SARD individuals, which achieved statistical significance in UCTD patients. However, there was no association between the levels of BAFF and any of the B cell phenotypes, whereas the IFN signature was positively associated with the proportion of T1T2 cells. Conclusions B cell phenotypic abnormalities precede the onset of clinical disease in ANA+ individuals and have a pattern suggesting ongoing activation through T-B collaboration.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 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) | 0.003 | 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".