{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:20:37Z","timestamp":1788175237956,"version":"build-2803163510"},"reference-count":38,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["European Union"],"award-info":[{"award-number":["European Union"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI21\/01159"],"award-info":[{"award-number":["PI21\/01159"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_dx-2025-0077_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Serious adverse drug reactions (SADRs) require robust causality assessment methods. Identifying the culprit drug relies on clinical history, causality algorithms, and\n                      <jats:italic>in\u00a0vitro<\/jats:italic>\n                      tests. The lymphocyte transformation test (LTT) is widely used, but flow cytometry has been proposed as an alternative due to LTT\u2019s limitations. This study evaluated the diagnostic performance of LTT and CD69 upregulation on T lymphocytes by flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dx-2025-0077_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 148 patients (150 SADRs) with at least a \u201cpossible\u201d algorithmic causality score (\u22654) were assessed using LTT and flow cytometry. Twenty-five healthy individuals served as negative controls. Over 98\u202f% of cases were organ-specific reactions, with drug-induced liver injury being most frequent (52.6\u202f%), and systemic antibiotics the most implicated drug group (29.7\u202f%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dx-2025-0077_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>400 suspected drugs were analyzed. LTT and flow cytometry were positive in 43 and 30\u202f% of patients, respectively. For cases with an algorithmic score\u22656, sensitivity increased to 50\u202f% for LTT and 33\u202f% for flow cytometry. Sensitivity varied by reaction type (LTT: 17\u201347\u202f%; flow cytometry: 20\u201338\u202f%) and drug group (LTT: 17\u201386\u202f%; flow cytometry: 18\u201350\u202f%). Combining both tests improved sensitivity to 50\u201363\u202f% by reaction type and 50\u2013100\u202f% by drug group. An algorithmic score\u22656 combined with both tests further increased overall sensitivity to 70\u202f%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_dx-2025-0077_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings show the added value of integrating multiple\n                      <jats:italic>in\u00a0vitro<\/jats:italic>\n                      diagnostic approaches with causality algorithms to improve culprit drug identification in organ-specific SADRs. Future studies are needed to validate these findings.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/dx-2025-0077","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:08:16Z","timestamp":1761844096000},"page":"492-501","source":"Crossref","is-referenced-by-count":1,"title":["Diagnostic performance of lymphocyte transformation test and flow cytometry in the identification of culprit drugs in organ-specific serious adverse drug reactions"],"prefix":"10.1515","volume":"13","author":[{"given":"Carmen","family":"Ruiz-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Immunology Department , 16268 La Paz University Hospital-IdiPAZ , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibtissam","family":"Akatbach-Bousaid","sequence":"additional","affiliation":[{"name":"Immunology Department , 16268 La Paz University Hospital-IdiPAZ , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Rogozina","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pharmacology Department , La Paz University Hospital-IdiPAZ, Universidad Aut\u00f3noma de Madrid , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Mart\u00edn-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pharmacology Department , La Paz University Hospital-IdiPAZ, Universidad Aut\u00f3noma de Madrid , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1lvarez","family":"Montero","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pharmacology Department , La Paz University Hospital-IdiPAZ, Universidad Aut\u00f3noma de Madrid , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon Pardo","family":"Puras","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pharmacology Department , La Paz University Hospital-IdiPAZ, Universidad Aut\u00f3noma de Madrid , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoraida","family":"Del Solar Moreno","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pharmacology Department , La Paz University Hospital-IdiPAZ, Universidad Aut\u00f3noma de Madrid , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorela C.","family":"Due\u00f1as L\u00f3pez","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pharmacology Department , La Paz University Hospital-IdiPAZ, Universidad Aut\u00f3noma de Madrid , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikel Urroz","family":"Elizalde","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pharmacology Department , La Paz University Hospital-IdiPAZ, Universidad Aut\u00f3noma de Madrid , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Mart\u00ednez","family":"Feito","sequence":"additional","affiliation":[{"name":"Immunology Department , 16268 La Paz University Hospital-IdiPAZ , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Gonz\u00e1lez-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Immunology Department , 16268 La Paz University Hospital-IdiPAZ , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4052-8876","authenticated-orcid":false,"given":"Elena","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Clinical Pharmacology Department , La Paz University Hospital-IdiPAZ, Universidad Aut\u00f3noma de Madrid , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"2026083110583440946_j_dx-2025-0077_ref_001","doi-asserted-by":"crossref","unstructured":"Pirmohamed, M, James, S, Meakin, S, Green, C, Scott, AK, Walley, TJ, et al.. 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