Anti-PD-L1 Augmentation of IFN-γ ELISpot Improves Detection of Culprit Drugs in Non-Immediate Drug Hypersensitivity: A Cohort Study.
retrospective_cohort · Level III
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- Record sourced from PubMed, PMID 42567500.
- Also identified by DOI 10.1016/j.jaip.2026.07.041.
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Abstract
The IFN-γ ELISpot assay identifies culprit drugs in non-immediate drug hypersensitivity reactions (DHRs), but sensitivity is reduced in certain clinical contexts, particularly with systemic corticosteroid use. To evaluate whether anti-PD-L1 supplementation increases detectable drug-specific T-cell responses in patients at higher risk of false-negative conventional ELISpot results. In this retrospective cohort study, 223 patients (450 drug-level tests) with SCARs and other non-immediate DHRs underwent paired ELISpot testing under conventional and anti-PD-L1-supplemented conditions. Anti-PD-L1 was applied selectively to patients with corticosteroid use, remote reaction history, or DRESS phenotype. Positivity was defined as ≥20 SFU per 10<sup>6</sup> PBMCs. Paired positivity was compared by McNemar's test and SFU magnitude by Wilcoxon signed-rank test, with pre-specified subgroup analyses by corticosteroid exposure, phenotype, and drug class. Anti-PD-L1 supplementation increased ELISpot positivity from 14.4% (65/450) to 35.3% (159/450), an absolute increase of 20.9% (94 additional positive tests; p<0.001). Conventional positivity was numerically lower in corticosteroid-treated patients (11.6% vs 18.5%, p=0.059), whereas anti-PD-L1-modified positivity was similar between groups (35.4% vs 34.7%, p=0.950). Augmented responses were consistent across all phenotypes and correlated with established causality scores. Among 114 patients tested against more than one distinct drug, positivity remained predominantly limited to a single drug per patient under both testing conditions. Anti-PD-L1 supplementation substantially increased detectable ELISpot reactivity. Although conventional positivity was numerically lower in corticosteroid-treated patients, positivity was similar between groups after anti-PD-L1 supplementation. While single-drug positivity predominated, some patients showed reactivity to two or more drugs under anti-PD-L1-supplemented conditions. Prospective multicenter validation is warranted.