The Lymphocyte Transformation Test was originally developed in the 1960s for evaluating histocompatible class II HLA antigens. The method was then modified for class II antigen typing and also applied extensively to detecting type IV allergies to drugs, metabolites, infectious organisms and metals. LTT became a common test for detection of allergy to beryllium, nickel, gold, cobalt, chromium and palladium. LTT to beryllium is now accepted as the “gold standard” for diagnosing berylliosis, a lung disease, in USA.

In 1994, Stejskal and colleagues published a modification of the LTT for detecting metal sensitivity – the MELISA test. The reason for the development of a modern in vitro testing tool was that Astra, a large Swedish pharmaceutical company needed a test for the diagnosis of occupational drug allergy for their workers exposed to dust containing beryllium during drug production.

By optimizing of the methodology of LTT, MELISA has improved both the specificity and the sensitivity of the test. Below are the four major changes that MELISA implements, in contrast with LTT.

  • MELISA uses a higher number of lymphocytes per test
  • The metal concentrations used have been chosen so that they are non-mitogenic and non-toxic
  • The test uses partial depletion of macrophages which restores the lymphocyte-monocyte balance so that it is similar to that in the blood
  • In addition to objective determination of lymphocyte proliferation by radio labelled thymidine, morphological examination gives an additional reading directly on the level of stimulated lymphocytes

The MELISA test was validated on 250 patients in 2003 and found to be reproducible, sensitive, specific and reliable for detecting metal sensitivity. To our knowledge, no other LTT except the widely published Beryllium-LTT, has been validated.