A Prospective Multi-Center Observational Trial to Evaluate a CMV-specific ELIspot Assay in Solid Organ Transplant (SOT) Recipients
Bibliographic record
Abstract
Introduction CMV replication in transplant recipients is primarily controlled by the T-cell response. We evaluated the role of a novel CMV-specific ELISPOT assay to predict protection against CMV infection in SOT recipients. Materials and Methods This was a multi-center (43 sites), prospective, observational study of kidney transplant recipients at risk for CMV. Subjects were enrolled either pre-transplant or during initial anti-viral prophylaxis. Clinical management was performed according to local institutional protocols. Cell-mediated immunity (CMI) was determined using an ELISPOT assay that evaluated responses to CMV-specific antigens IE-1 and pp65, from the capture of IFN-γ enumerated as spot counts (T-SPOT.CMV, Oxford Immunotec). CMV CMI and quantitative PCR (Roche Cobas) were assessed at 1, 2, 3, 4 and 6 months following completion of anti-viral prophylaxis. CMV events necessitated a change in anti-viral therapy or immunotherapy to be eligible for analysis. The endpoint was the first occurrence of CMV disease or CMV infection after the completion of prophylaxis. T-SPOT values taken at the completion of prophylaxis were analyzed to predict protection against CMV up to 1 year post-transplant. Results Of the 597 subjects enrolled, 411 were included in the analysis based on having valid TSPOT counts within ± 30 days of the completion of prophylaxis and a non-missing date of completion of prophylaxis. Of the 411 subjects, 203 were R+ (49%), 178 were D+/R- (43%), 22 were D-/R- (5%) and 8 subjects had unknown CMV serostatus. The majority of patients were white (67%), male (62%), and median age was 52. Most patients received 3 months of antiviral prophylaxis (55%) vs 6 months of prophylaxis (44%). 3 subjects did not receive any antiviral prophylaxis (1%). Of the 411 eligible subjects, 87 had an IE-1 response of > 50 spots at the completion of prophylaxis. In this group, 1 of 87 developed CMV infection following the completion of prophylaxis, resulting in a negative predictive value (NPV) against the occurrence of a CMV event of 98.9% (p=0.0014) (see Figure 1). Using the same cut-off for pp65, the NPV against the occurrence of a CMV event was 96.5% (p=<0.0001) (see Figure 2).Conclusion To date, this is the largest prospective study on the use of IFN-γ release assays to predict the risk of CMV infection in organ transplant recipients. We show that T-SPOT.CMV IE-1 and pp65 spot counts > 50 at the completion of prophylaxis are a significant predictor of protection against CMV infection/disease in SOT recipients.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".