Pilot Study to Improve In Vitro Identification of Culprit Drugs in SJS/TEN Using Granzyme B and Granulysin Secretion...

Area of Science:

• Immunology
• Pharmacology
• Dermatology

Background:

• Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions (SCARs).
• Accurate identification of the causative drug is crucial but challenging.
• Current in vitro tests like the lymphocyte transformation test (LTT) have limited sensitivity.

Purpose of the Study:

• To evaluate the measurement of granulysin (Gr) and granzyme B (GZB) secretion from drug-stimulated peripheral blood mononuclear cells (PBMCs) for identifying culprit drugs in SJS/TEN.
• To compare the diagnostic performance of Gr/GZB detection with the conventional LTT.

Main Methods:

• PBMCs from 12 SJS/TEN patients were incubated with suspected drugs.
• Lymphocyte transformation test (LTT), Gr, and GZB detection assays were performed on days 3 and 6.
• Granulysin and granzyme B levels were quantified, and receiver operating characteristic (ROC) curve analysis defined cut-off values.

Main Results:

• Granzyme B (GZB) detection on day 3 showed higher sensitivity (8/12) than LTT (6/12).
• Combining GZB and granulysin (Gr) detection improved the positive rate to 10/12.
• ROC analysis indicated higher areas under the curve (AUCs) for cytokine assays, especially GZB at day 3, compared to LTT.

Conclusions:

• GZB and Gr detection in PBMC cultures is a more sensitive and specific method for identifying culprit drugs in SJS/TEN than LTT.
• GZB detection on day 3 offers a shorter assay duration, avoids radioactive labeling, and shows superior diagnostic performance.
• This cytokine-based approach provides a practical and safer alternative for drug causality assessment in SCARs.