AI-09 T follicular helper (Tfh) cells are increased in asymptomatic anti-nuclear antibody (ANA)<sup>+</sup> individuals and appear to play a role in epitope spreading
Bibliographic record
Abstract
Background The diagnosis of Systemic Autoimmune Rheumatic Diseases (SARD), including Systemic Lupus Erythematosus (SLE), relies on the presence of ANAs, many of which can be detected years before clinical manifestations. However, ANAs are also seen in healthy individuals most of whom will not develop SARD. A number of cellular immune changes are seen in SARD, and thus could constitute potential biomarkers/treatment targets for SARD, however it is not known at what point in disease progression these develop. Methods Healthy ANA- controls (n=32) and ANA+ (≥1:160 by immunofluorescence) participants with no (asymptomatic ANA+, n=61), at least one (UCTD, n=35), or meeting SARD classification criteria (n=59) were recruited. Peripheral blood cellular immunological changes were assessed by flow cytometry. Results Consistent with previous reports, SARD patients had increased proportions of activated B cells (CD86+ or CD95+) and in the SLE patient subset there were increased proportions of plasma cells/plasmablasts, as compared to ANA- controls. SARD patients also had reduced proportions of iNKT and IFN-γ producing cells, as well as, increased proportions of memory Tfh (CD4+CXCR5hiPD1hi) and T regulatory (Treg, CD4+FOXP3+HELIOS+) cells, especially in the SLE and Sjogren’s Disease patient subsets. In asymptomatic ANA+ individuals and UCTD patients, similar increases in the proportion of activated B cells, Tfh, and Treg cells, and decreases in the proportion of iNKT and IFN-γ producing cells were seen to those in SARD. In asymptomatic ANA+ individuals and SARD patients, the extent of serologic changes (number of specific ANAs detected by Bioplex® 2200 ANA screening system) positively correlated with activation in the switched memory B cell compartment and the proportion of Tfh cells, with the later being an independent predictor of serologic status in a multivariate analysis. However, significantly elevated levels of Tfh cells could still be seen in asymptomatic ANA+ individuals who lacked specific ANAs. Consistent with a role for Tfh cell in ANA production there was a strong correlation between the proportion of Tfh and plasma cells in asymptomatic ANA+ individuals. In preliminary studies, the majority of Tfh cells in asymptomatic ANA+ and UCTD patients were Tfh2 cells, with a trend to increased proportions of Tfh2 cells and decreased proportions Tfh17 cells as compared to active SLE patients. Conclusions Tfh cells appear to play an important role in the development of a positive ANA and in the epitope spreading that may accompany disease progression, and therefore constitute a promising target for treatment of early disease.
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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 | 0.001 | 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) | 0.005 | 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".