Soluble Donor DNA and Islet Injury After Transplantation
Bibliographic record
Abstract
INTRODUCTION: A large proportion of clinical islet transplant recipients fail to initially achieve or sustain meaningful independence from exogenous insulin use. We hypothesized that immediate allograft injury is a key constraint on independence from exogenous insulin use. METHODS: Standard human leukocyte antigen genotyping was reviewed to identify nonshared polymorphisms between 21 prospectively recruited islet transplant recipients from a single institution and their respective donors. Human leukocyte antigen polymorphism-specific quantitative polymerase chain reaction was used to quantify donor DNA shed into blood by injured islets from serial sera acquired over the first 10 days postprocedure and examined for correlation with achievement of insulin independence. RESULTS: Nearly fourfold higher serum concentrations of donor DNA were detected in subjects whose grafts failed to generate insulin independence. The median for the average area under the curve in recipients who did and did not achieve insulin independence was 12 (range, 1-61) and 45 (range, 14-255) donor genome equivalents (gEq)-day/mL (p=0.03), respectively. CONCLUSIONS: These findings represent the first direct testing of allograft injury in humans undergoing islet cell transplantation. Injury to donor islets very soon after transplantation may represent an important barrier to achieving insulin independence other than adaptive immune responses targeting allografts at later times. In addition, soluble donor DNA merits further development as a quantifiable biomarker to evaluate new interventions aimed at mitigating immediate islet injury.
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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 | 0.000 | 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 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".