Lymphocyte transformation test for drug allergy detection When does it work?

被引:17
作者
Glaessner, Andreas [1 ]
Dubrall, Diana [1 ,2 ]
Weinhold, Leonie [2 ]
Schmid, Matthias [2 ]
Sachs, Bernhardt [1 ,3 ]
机构
[1] Fed Inst Drugs & Med Devices BfArM, Res Div, Bonn, Germany
[2] Univ Hosp Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany
[3] Univ Hosp Aachen, Dept Dermatol & Allergy, Aachen, Germany
关键词
ENZYME-LINKED IMMUNOSPOT; IN-VITRO DETECTION; HYPERSENSITIVITY REACTIONS; T-CELLS; DIAGNOSIS; PROLIFERATION; RESPONSES; GAMMA; CARBAMAZEPINE; EOSINOPHILIA;
D O I
10.1016/j.anai.2022.06.014
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: The lymphocyte transformation test (LTT) is an in vitro test system for the detection of a sensitiza-tion in the context of allergies to drugs. Its reported sensitivity varies largely and seems to be affected by differ-ent parameters. In review articles, the average LTT performance was often calculated by combining overall mean sensitivities of various published studies, but without considering different patient characteristics or varying patient numbers per publication.Objective: To investigate the impact of different patient-specific and methodological parameters on the sensitiv-ity of the LTT based on data on the level of the individual patient extracted from single studies. Methods: We performed an advanced literature search in PubMed and screened the identified publications according to previously defined inclusion criteria. In total, individual patient data from 721 patients were extracted from 30 studies. Random-effects meta-regression analyses were performed.Results: The analysis indicate that the enzyme-linked immunosorbent assay-based read-out is more sensitive compared with the classical radioactivity method (enzyme-linked immunosorbent assay: 80% vs radioactivity: 66%; P = .08). Interestingly, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitiv-ity syndrome is associated with a higher probability of a positive LTT test result compared with other investi-gated clinical phenotypes ("drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome" vs "bullous reaction"; odds ratio, 2.52; P value = .003). Our analysis also revealed an impact of the time to testing period after the occurrence of the allergic event ("< 2 weeks" vs "2 weeks-2 months"; odds ratio, 2.12; P value = .03).Conclusion: The read-out method and relevant clinical parameters affect the sensitivity of the LTT. These find-ings are based on a meta-analysis providing a higher level of evidence than a single study or previous reviews not considering individual patient data.(c) 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. This is an open access arti-cle under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
引用
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页码:497 / +
页数:13
相关论文
共 52 条
[1]   Lymphocyte Transformation Test (LTT) in Allergy to Benznidazole: A Promising Approach [J].
Andreina Marques-Mejias, M. ;
Cabanas, Rosario ;
Ramirez, Elena ;
Dominguez-Ortega, Javier ;
Fiandor, Ana ;
Trigo, Elena ;
Quirce, Santiago ;
Bellon, Teresa .
FRONTIERS IN PHARMACOLOGY, 2019, 10
[2]   Assessment of drug causality in SJS']JS/TEN: Concordance between lymphocyte transformation test and ALDEN [J].
Bellon, Teresa ;
Rodriguez-Martin, Sara ;
Cabanas, Rosario ;
Ramirez, Elena ;
Lerma, Victoria ;
Gonzalez-Herrada, Carlos ;
Gonzalez, Olga ;
Sendagorta, Elena ;
Fiandor, Ana ;
de Abajo, Francisco J. .
ALLERGY, 2020, 75 (04) :956-959
[3]   Guideline to Allergy Diagnosis of Hypersensitive Reactions to Medicines [J].
Brockow, Knut ;
Przybilla, Bernhard ;
Aberer, Werner ;
Bircher, Andreas J. ;
Brehler, Randolf ;
Dickel, Heinrich ;
Fuchs, Thomas T. ;
Jakob, Thilo T. ;
Lange, Lars ;
Pfuetzner, Wolfgang ;
Mockenhaupt, Maja ;
Ott, Hagen ;
Pfaar, Oliver ;
Ring, Johannes ;
Sachs, Bernhardt ;
Sitter, Helmut ;
Trautmann, Axel ;
Treudler, Regina ;
Wedi, Bettina ;
Worm, Margitta ;
Wurpts, Gerda ;
Zuberbier, Torsten ;
Merk, Hans F. .
ALLERGO JOURNAL, 2015, 24 (03) :44-55
[4]   Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment [J].
Cabanas, R. ;
Calderon, O. ;
Ramirez, E. ;
Fiandor, A. ;
Caballero, T. ;
Heredia, R. ;
Herranz, P. ;
Madero, R. ;
Quirce, S. ;
Bellon, T. .
CLINICAL AND EXPERIMENTAL ALLERGY, 2018, 48 (03) :325-333
[5]   In vitro lymphocyte proliferation in the diagnosis of allergy to phenoxymethylpenicillin [J].
Cederbrant, K ;
Stejskal, V ;
Broman, P ;
Lindkvist, L ;
Sundell, K .
ALLERGY, 1998, 53 (12) :1155-1161
[6]   Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects [J].
Cederbrant, K ;
Marcusson-Ståhl, M ;
Hultman, P .
CLINICAL AND EXPERIMENTAL ALLERGY, 2000, 30 (10) :1450-1459
[7]   International Consensus on drug allergy [J].
Demoly, P. ;
Adkinson, N. F. ;
Brockow, K. ;
Castells, M. ;
Chiriac, A. M. ;
Greenberger, P. A. ;
Khan, D. A. ;
Lang, D. M. ;
Park, H. -S. ;
Pichler, W. ;
Sanchez-Borges, M. ;
Shiohara, T. ;
Thong, B. Y. -H. .
ALLERGY, 2014, 69 (04) :420-437
[8]   Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis [J].
Duval, S ;
Tweedie, R .
BIOMETRICS, 2000, 56 (02) :455-463
[9]  
Gex-Collet C, 2005, J INVEST ALLERG CLIN, V15, P293
[10]  
Halevy S, 2008, ISR MED ASSOC J, V10, P865