Lymphocyte transformation test

Considering the magnitude of the problem of delayed hypersensitivity reactions to drugs and the difficulties associated wifli flie lymphocyte transformation test, there is a need to develop sensitive and specific tests that are more easily and quickly carried out, widely apphcable to flie many forms of delayed drug reactions and valuable for use in the clinic as well as the research laboratory. 

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Positive lymphocyte transformation test and lymphocyte activation tests... 

RCM-related T-cell activity may be assessed in vitro by lymphocyte transformation test [19, 24]. In addition, CD69 upregulation (lymphocyte activation test) was observed in patients with a positive lymphocyte transformation test [24, 39]. These tests appear to be a promising tool to identify drug-reactive T cells in the peripheral blood of patients with RCM-induced drug-hypersensitivity reactions. However, the sensitivity and specificity remain unknown and, therefore, these tests cannot be recommended for routine use yet, but further research on the specificity and sensitivity is indicated. 

For in vitro testing of nickel contact sensitivity, the lymphocyte transformation test and leucocyte migration inhibition test have been used [370]. 

A 60-year-old woman with normal liver function tests developed acute hepatitis 6 weeks after starting to take gliclazide. No viruses, autoimmune factors, or metabolic factors that could have caused hepatitis could be found. A lymphocyte transformation test was not performed. A liver biopsy was compatible with drug-related acute hepatitis. When gliclazide was withdrawn she improved. She took glibenclamide and recovered fully within 6 weeks. 

After 18 intramuscular injections of Arumalon, a 62-year-old woman with degenerative hip-joint changes developed a severe illness, with fever up to 39 C, swellings of the finger, hand, and knee joints, a rash, leukopenia (1.9 X 10 /1), thrombocytopenia (113 x 10 /1), and increased transaminases and lactate dehydrogenase activity (25). There was a positive lymphocyte transformation test with Arumalon and its constituents, and Arumalon-specific antibodies in the cultured... 

A 12-year-old boy developed a maculopapular rash on two occasions after taking carbamazepine (69). A patch test was positive, but an in vitro lymphocyte transformation test was negative. However, T cells incubated with carbamazepine produced an excess of interferon-gamma. 

A man developed acute generalized exanthematous pustulosis while taking furosemide (18). A positive lymphocyte transformation test suggested an immunological mechanism. 

Mantani N, Kogure T, Sakai S, Goto H, Shibahara N, Kita T, Shimada Y, Terasawa K. Incidence and clinical features of Uver injury related to Kampo (Japanese herbal) medicine in 2,496 cases between 1979 and 1999 problems of the lymphocyte transformation test as a diagnostic method. Phytomedicine 2002 9(4) 280-7. 

Twenty patients with a prior history of generalized and/ or local skin reactions after local anesthetics were examined with intradermal testing and patch testing in 10 of them a lymphocyte transformation test was performed to investigate whether they had T cell sensitization to local anesthetics, which might have been responsible for their symptoms (36). Only two had a positive intradermal test, whereas six had a positive patch test and six had a positive lymphocyte transformation test, suggesting that allergic skin symptoms could be mediated by T cells in some patients who do not have evidence of an IgE-mediated reaction. 

Alexander S, Forman L. Which of the drugs caused the rash Or the value of the lymphocyte transformation test in eruptions caused by nalidixic acid. Br J Dermatol 1971 84(5) 429-34. 

Al-Tawil NG, Marcusson JA, Moller E. Lymphocyte transformation test in patients with nickel sensitivity an aid to diagnosis. Acta Derm Venereol 1981 61(6) 511-15. 

A 20-year-old man with abdominal trauma received a single dose of piperacillin (1 g) followed by nine doses of imipenem + cilastatin (500 mg tds for 3 days) and 2 weeks later developed jaundice, fatigue, and pruritus (94). A liver biopsy showed centrilobular cholestasis, portal infiltration with eosinophils, and cholangitis. Lymphocyte transformation tests for piperacillin and imipenem/cilastatin were positive, suggesting an immunological mechanism. He made a full clinical and biochemical recovery after 3 months. 

Agranulocytosis and liver injury have been described in a patient with Reiter s syndrome who took pyrazinobuta-zone for 6 weeks (20). Other causes of agranulocytosis and hepatic damage were excluded and a lymphocyte transformation test showed significant lymphocyte proliferation in response to pyrazinobutazone. 

Zonisamide-induced lupus erythematosus has been reported in a 5-year-old child taking zonisamide and etho-suximide (15). He had raised titers of antinuclear antibodies and anti-DNA antibodies and presented with fever, pericarditis, pleurisy, and arthralgia. Clinical recovery and a reduction in the anti-DNA-antibody titer promptly followed withdrawal. A lymphocyte transformation test against zonisamide was positive. 

Denman EJ, Denman AM. The lymphocyte transformation test and gold hypersensitivity. Ann Rheum Dis 1968 27 582-588. 

The situation with in vitro models for predicting ACD, unlike its in vivo counterpart, is less complicated than that for ICD because there are very few in vitro systems which have even been proposed for ACD testing. This is also a consequence of the complexity of this disease since ACD involves the interaction of many organ systems, which cannot be properly simulated in any currently available cell or tissue culture model. Nevertheless, two assays that have shown some promise for predicting ACD with certain classes of allergens are the lymphocyte transformation test and the macrophage migratory inhibition test. 

Li Q, Wang ZY, Inagaki H, et al. 1995. Evaluation of contact sensitivity to formaldehyde and tetramethylthiuram monosulfide using a modified lymphocyte transformation test. Toxicology 104 17-23. 

A number of experiments performed thereafter were supportive for the immune-based etiology of zimeldine-induced adverse effects (Kristofferson Nilsson, 1989). Three individuals occupationally exposed to zimeldine developed allergy to the compound and showed positive patch and skin prick tests and positive response to zimeldine in the lymphocyte transformation test. Patients with a history of zimeldine-induced disease showed marked lymphocyte transformation test responses to zimeldine as well as two metabolites (norzimeldine and CPP200). These findings indicate that zimeldine may be immunogenic indeed, zimeldine has been shown to be positive in the popliteal lymph node assay, based on cell numbers and including germinal centre formation and production of IgM and IgG antibodies (Thomas et al., 1989). 

When a patient suffers from a certain autoimmune disease and one suspects the person to be exposed to a certain environmental factor, few possibilities exist to prove exposure. Several in vitro or in vivo tests, such as skin tests, serological tests, and the lymphocyte transformation test (LTT), can be performed to demonstrate a sensitization to a certain chemical (Choquet-Kastylevsky et al., 2001 Pichler, 2003). 

Denman EJ, Denman AM. The lymphocyte transformation test and gold hypersensitivity. Ann Rheum Dis 1968 27 582-588. Derot M, Kahn J, Mazalton A, Peyrafort J. Fatal anuric nephritis with associated chrysocyanosis following gold therapy. Bull Soc Med Hop Paris 1954 70 234-239. 

Drugs with Potential to Activate According to the P-I Concept. To assess whether a new drug candidate can activate T cells according to the p-i concept, a battery of T-cell clones derived from drug allergic patients may be used in so-called lymphocyte transformation tests (LTTs) (Beeler and Pichler, 2007). Since the affinity involved in these interactions is very low, LTTs would also allow identifying cross-reactivity. 

A structurally related saponin squarroside A vide supra) has been isolated from Acanthophyllum squarrosum [60]. This saponin of gypsogenin contains one more xylose linked to C-3 of the glucuronic acid. This molecule showed a concentration dependent immunomodulatory effect in the in vitro lymphocyte transformation test. 

Saponins from the roots of Acanthophyllum squarrosum showed a concentration dependent immunomodulatory effect [60] in the in vitro lymphocyte transformation test. 

A variety of techniques have been employed to assess the immune response to beryllium. Ho vever, the ease, sensitivity, and specificity have made the lymphocyte proliferation assay using H-thymidine the standard technique (Rossman et al. 1988, Mroz et al. 1991). In the past, this technique has been referred to as the lymphocyte transformation test (LTT), but transformation is an older term that is no longer applicable. The cells respond by proliferating (a normal process) and are not transformed, which today implies a malignant process. Hence, the test is currently known as the lymphocyte proliferation test (LPT). 

Meoz NM, Kreiss K, Lezotte KD, Campbell PA. and Newman LS (1991) Reexamination of the blood lymphocyte transformation test in the diagnosis of chronic beryllium disease. J Allergy Clin Immunol 88 54-60. 

In the lymphocyte transformation test, aqueous extracts of shiitake were able to enhance the proliferation of rat thymocytes directly and act as costimulators in the presence of the T-mitogen phytohaemagglutinin (PHA) (Israilides et al. 2008). 

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