Elevated ADA2 Enzyme Activity at the Onset of Chronic Graft-versus-Host Disease in Children
Bibliographic record
Abstract
Adenosinergic signaling has potent, context-specific effects on immune cells, particularly on the dysregulation of lymphocytes. This in turn may have a role in immune activation and loss of tolerance in such diseases as chronic graft-versus-host disease (chronic GVHD). We assessed whether changes in the enzymatic activity of adenosine deaminase 2 (ADA2), an enzyme that depletes adenosine in the extracellular space via conversion to inosine, may be associated with the onset of chronic GVHD. ADA2-specific enzyme activity was measured in plasma samples from 230 pediatric hematopoietic stem cell transplantation (HSCT) recipients enrolled on the Applied Biomarkers of Late Effects of Childhood Cancer (ABLE)/Pediatric Blood and Marrow Transplant Consortium (PBMTC) 1202 study and compared between patients developing chronic GVHD and those not developing chronic GVHD within 12 months of transplantation. ADA2 and its relationships with 219 previously measured plasma-soluble proteins, metabolites, and immune cell populations were evaluated as well. Plasma ADA2 enzyme activity was significantly elevated in pediatric HSCT recipients at the onset of chronic GVHD compared to patients without chronic GVHD and was not associated with prior history of acute GVHD or generalized inflammation as measured by C-reactive protein concentration. ADA2-specific enzyme activity met our criteria as a potential diagnostic biomarker of chronic GVHD (effect ratio ≥1.30 or ≤.75; area under the receiver operating characteristic curve ≥.60; P < .05) and was positively associated with markers of immune activation previously identified in pediatric chronic GVHD patients. These results support the potential of ADA2 enzyme activity, in combination with other biomarkers and subject to future validation, to aid the diagnosis of chronic GVHD in children post-HSCT.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".