Some science behind the scenes

LTT test

The Lymphocyte Transformation Test - LTT test can reveal a sensitization of T-cells by an enhanced proliferative response of peripheral blood mononuclear cells to a certain substance.

It can be used for 'Type IV' allergies and uses antigen specific sensitised leukocytes.  Thus there is no testing of antibodies and the test has proved very accurate.  So called Type IV allergies are delayed allergies, reactions only occur 2 - 5 days after allergen contact.  Naturally such a separation between the symptom and trigger makes things difficult but it is not uncommon.  This type of allergic response often occurs in dentistry, when the dental metals cause a reaction many days after the actual work undertaken.  After a sensitisation stage, the metals bind to body proteins and then these metallo-proteins are detected by the immune system and tagged as foreign, the immune system then activates the killer cells to consume the allergen.  Decay products so formed may cause various skin lesions.  Lymphocytes react directly with the allergen, as such all usual medical tests relying on IgE antibody tests will not work, only LTT tests are appropriate.

The same sorts of tests can be used to find out if a metal implant is causing problems.

There has also been work on extending the uses of this diagnostic aid to the identification not just of allergens but diseases. 

Diagnosis of active Lyme borreliosis (LB) remains a challenge in clinically ambiguous, serologically indeterminant, and polymerase chain reaction-negative patients. Lymphocyte transformation tests (LTTs) have been applied to detect specific cellular immune reactivity, but their clinical application has been severely hampered by the poorly defined Borrelia antigens and nonstandardized LTT formats used. But work is ongoing to use 'well-defined recombinant Borrelia-specific antigens'. [PMID:16876371]

The LTT test has also been shown to work quite successfully at identifying allergies to pharmaceuticals.

Clin Exp Allergy. 1997 Feb;27(2):175-81.  The lymphocyte transformation test for the diagnosis of drug allergy: sensitivity and specificity.  Nyfeler B1, Pichler WJ.

BACKGROUND:  The diagnosis of a drug allergy is mainly based upon a very detailed history and the clinical findings. In addition, several in vitro or in vivo tests can be performed to demonstrate a sensitization to a certain drug. One of the in vitro tests is the lymphocyte transformation test (LTT).

OBJECTIVE: To evaluate the sensitivity and specificity of the LTT, 923 case histories of patients with suspected drug allergy in whom a LTT was performed were retrospectively analysed.

METHODS: Based on the history and provocation tests, the probability (P) of a drug allergy was estimated to be > 0.9, 0.5-0.9, 0.1-0.5 or < 0.1, and was put in relation to a positive or negative LTT.

RESULTS:  Seventy-eight of 100 patients with a very likely drug allergy (P > 0.9) had a positive LTT, which indicates a sensitivity of 78%. If allergies to betalactam-antibiotics were analysed separately, the sensitivity was 74.4%. Fifteen of 102 patients where a classical drug allergy could be excluded (P < 0.1), had nevertheless a positive LTT (specificity thus 85%). The majority of these cases were classified as so-called pseudo-allergic reaction to NSAIDs. Patients with a clear history and clinical findings for a cotrimoxazole-related allergy, all had a positive LTT (6/6), and in patients who reacted to drugs containing proteins, sensitization could be demonstrated as well (i.e. hen's egg lysozyme, 7/7). In 632 of the 923 cases, skin tests were also performed (scratch and/or epicutaneous), for which we found a lower sensitivity than for the LTT (64%), while the specificity was the same (85%).

CONCLUSION:  Although our data are somewhat biased by the high number of penicillin allergies and cannot be generalized to drug allergies caused by other compounds, we conclude that the LTT is a useful diagnostic test in drug allergies, able to support the diagnosis of a drug allergy and to pinpoint the relevant drug.

PMID: 9061217