Analysis of IgVH-specific, CXCR4-specific and CXR5-specific mRNA transcripts in individual peripheral blood B cells of patients with primary Sjögren's syndrome and normal healthy subjects
Bibliographic record
Abstract
Disturbances in peripheral B-cell homeostasis have been found to be characteristic of primary Sjögren's syndrome (pSS). Abnormal chemokine receptor expression has been proposed to be involved in the pathogenesis of autoimmune diseases. This study aimed to further delineate disturbances in peripheral CD27 naive and CD27 memory B cells and their expression of chemokine receptors in pSS. Isotype-specific immunoglobulin heavy chain (IgH) transcripts as well as chemokine receptor (CXCR4 and CXCR5) specific mRNA transcripts were analyzed in single-sorted CD19 D27 naïve and CD19 CD27 memory B cells from pSS patients and normal healthy subjects (NHS). A significantly higher frequency of B cells coexpressing μ, α, and/or γ chain transcripts were found in pSS patients compared with controls (58.0% versus 14.3%, P < 0.0001). Contrasting the findings in NHS, peripheral memory B cells in pSS patients were characterized by heavily mutated IgV H transcripts (mutational frequency, 8.6% versus 4.4%; P < 0.0001). Notably, this included significantly enhanced mutational frequencies of Cμ-transcripts (9.6% in pSS versus 2.5% in NHS, P < 0.0001). A CD27 memory-type B-cell subpopulation expressing mutated Cμ-transcripts was exclusively found in pSS patients. Moreover, a significantly enhanced frequency of CXCR4-mRNA-positive CD27 naive B cells was found in pSS patients when compared with NHS (36.0% versus 18.1%, P < 0.0001). Altogether, B-cell hyperactivity and abnormalities in peripheral B-cell memory are characteristic of patients with pSS. Differential expression of chemokine receptors appear to be involved in disturbances of peripheral B-cell homoestasis in pSS.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".