Lin<sup>−</sup>CD117<sup>+</sup>CD34<sup>+</sup>FcεRI<sup>+</sup> progenitor cells are increased in chronic spontaneous urticaria and predict clinical responsiveness to anti‐<scp>IgE</scp> therapy
Bibliographic record
Abstract
Abstract Background Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterized by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineage − CD34 hi CD117 int/hi FcεRI + cells in blood have previously been shown to represent a mast cell precursor. Methods We enumerated FcεRI − , FcεRI + and FcεRI hi lineage − CD34 + CD117 + cells using flow cytometry in blood of patients with CSU ( n = 55), including 12 patients receiving omalizumab and 43 not receiving omalizumab ( n = 43). Twenty‐two control samples were studied. Disease control and patient response to omalizumab was evaluated using the urticaria control test. We performed single‐cell RNA sequencing (scRNA‐Seq) on lineage − CD34 hi CD117 hi blood cells from a subset of patients with CSU ( n = 8) and healthy controls ( n = 4). Results CSU patients had more lineage − CD34 + CD117 + FcεRI + blood cells than controls. Lineage − CD34 + CD117 + FcεRI + cells were significantly higher in patients with CSU who had an objective clinical response to omalizumab when compared to patients who had poor disease control 90 days after initiation of omalizumab. scRNA‐Seq revealed that lineage − CD34 + CD117 + FcεRI + cells contained both lymphoid and myeloid progenitor lineages, with omalizumab responsive patients having proportionally more myeloid progenitors. The myeloid progenitor lineage contained small numbers of true mast cell precursors along with more immature FcεRI − and FcεRI + myeloid progenitors. Conclusion Increased blood CD34 + CD117 + FcεRI + cells may reflect enhanced bone marrow egress in the setting of CSU. High expression of these cells strongly predicts better clinical responses to the anti‐IgE therapy, omalizumab.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.001 | 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; both teacher heads agree on what is shown here.
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".