Altered Homeostasis of Regulatory T Lymphocytes and Differential Regulation of STAT1/STAT5 in CD4+ T Lymphocytes in Childhood-onset Systemic Lupus Erythematosus
Bibliographic record
Abstract
OBJECTIVE: Childhood-onset systemic lupus erythematosus (cSLE) is usually a more severe and aggressive disease than adult-onset SLE (aSLE), but cellular and subcellular reasons for these differences are not well understood. The present study analyzed Th subsets, STAT1/STAT5 signaling response, and cytokine profiles of cSLE. METHODS: FOXP3+ regulatory (Treg) and effector Th subsets, expression and phosphorylation of STAT1/STAT5 in Th, and cytokine profiles were measured in the peripheral blood of patients with cSLE and healthy controls (HC), using flow cytometry and immunoassay on a biochip. RESULTS: Significant correlation between expression of the activation marker HLA-DR and decreased Th counts, an increase in the percentage of FOXP3+ Th, and a decrease in the activated Treg (aTreg) subset among them were found in cSLE. In contrast to our previous findings in aSLE, no significant differences in percentages and a significant decrease in the numbers of the naive-resting Treg (rTreg) subset compared to HC were found. The percentages of CD25- cells, possibly reflecting interleukin 2 depletion, were significantly increased in cSLE aTreg, but not in the rTreg subset. Consistent with the results of our previous studies in aSLE, increased expression of STAT1, along with significant correlation between decreased Th counts and their increased basal phosphorylation of STAT5, were also found in cSLE. CONCLUSION: Our results suggest that the key difference in Treg homeostasis between cSLE and aSLE is in the rTreg subset. However, perturbed aTreg homeostasis, increased levels of STAT1 protein, and homeostatic STAT5 signaling appear to be intrinsic characteristics of the disease, present in cSLE and aSLE alike.
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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) | 0.001 | 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".