Diagnostic performance of lymphocyte transformation test and flow cytometry in the identification of culprit drugs in organ-specific serious adverse drug reactions.

Abstract

Objectives: Serious adverse drug reactions (SADRs) require robust causality assessment methods. Identifying the culprit drug relies on clinical history, causality algorithms, and in vitro tests. The lymphocyte transformation test (LTT) is widely used, but flow cytometry has been proposed as an alternative due to LTT's limitations. This study evaluated the diagnostic performance of LTT and CD69 upregulation on T lymphocytes by flow cytometry.

Methods: A total of 148 patients (150 SADRs) with at least a "possible" algorithmic causality score (≥4) were assessed using LTT and flow cytometry. Twenty-five healthy individuals served as negative controls. Over 98 % of cases were organ-specific reactions, with drug-induced liver injury being most frequent (52.6 %), and systemic antibiotics the most implicated drug group (29.7 %).

Results: 400 suspected drugs were analyzed. LTT and flow cytometry were positive in 43 and 30 % of patients, respectively. For cases with an algorithmic score≥6, sensitivity increased to 50 % for LTT and 33 % for flow cytometry. Sensitivity varied by reaction type (LTT: 17-47 %; flow cytometry: 20-38 %) and drug group (LTT: 17-86 %; flow cytometry: 18-50 %). Combining both tests improved sensitivity to 50-63 % by reaction type and 50-100 % by drug group. An algorithmic score≥6 combined with both tests further increased overall sensitivity to 70 %.

Conclusions: These findings show the added value of integrating multiple in vitro diagnostic approaches with causality algorithms to improve culprit drug identification in organ-specific SADRs. Future studies are needed to validate these findings.