Pichler W J, Tilch J
Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Bern, 3010-Bern, Switzerland.
Allergy. 2004 Aug;59(8):809-20. doi: 10.1111/j.1398-9995.2004.00547.x.
Diagnosis of drug hypersensitivity is difficult, as an enormous amount of different drugs can elicit various immune-mediated diseases with distinct pathomechanism. The lymphocyte transformation test (LTT) measures the proliferation of T cells to a drug in vitro--from which one concludes to a previous in vivo reaction due to a sensitization. This concept of the LTT has been confirmed by the generation of drug-specific T-cell clones and the finding that drugs can directly interact with the T-cell receptor, without previous metabolism or need to bind to proteins. In this review, technical aspects and usefulness of this test for the diagnosis of drug hypersensitivity are discussed. The main advantage of this test is its applicability with many different drugs in different immune reactions, as drug-specific T cell are almost always involved in drug hypersensitivity reactions. Its main disadvantages are that an in vitro proliferation of T cells to a drug is difficult to transfer to the clinical situation and that the test per se is rather cumbersome and technically demanding. In addition, its sensitivity is limited (for beta-lactam allergy it is in the range of 60-70%), - although at least in our hands - it is higher than of other tests for drug hypersensitivity diagnosis. Consequently, drug hypersensitivity diagnosis needs to rely on a combination of history and different tests, as none of the single tests available has per se a sufficiently good sensitivity. Within this setting, the LTT has proven to be a useful test for the diagnosis of drug hypersensitivity reactions and helped to better understand these reactions. Further work on the simplification of this test and systematic evaluation of its sensitivity and specificity in some main groups of drugs are necessary to make this test more widely available.
药物超敏反应的诊断很困难，因为大量不同的药物可引发具有不同发病机制的各种免疫介导疾病。淋巴细胞转化试验（LTT）可在体外检测T细胞对药物的增殖情况，由此推断之前因致敏而发生的体内反应。药物特异性T细胞克隆的产生以及药物可直接与T细胞受体相互作用（无需预先代谢或与蛋白质结合）这一发现证实了LTT的这一概念。在这篇综述中，将讨论该试验在药物超敏反应诊断中的技术方面及实用性。该试验的主要优点是它适用于不同免疫反应中的多种不同药物，因为药物特异性T细胞几乎总是参与药物超敏反应。其主要缺点是T细胞在体外对药物的增殖情况难以转化为临床情况，而且该试验本身相当繁琐且对技术要求较高。此外，其敏感性有限（对于β-内酰胺类过敏，其敏感性在60%-70%范围内），尽管至少在我们的经验中，它比其他药物超敏反应诊断试验的敏感性更高。因此，药物超敏反应的诊断需要依靠病史和不同检测方法的结合，因为现有的单一检测方法本身都没有足够好的敏感性。在此背景下，LTT已被证明是诊断药物超敏反应的一项有用检测方法，并有助于更好地理解这些反应。有必要进一步开展工作简化该试验，并对其在某些主要药物组中的敏感性和特异性进行系统评估，以使该试验能更广泛地应用。
