MELISA® (MEmory Lymphocyte Immuno-Stimulation Assay) is a modified, optimised and clinically validated version of lymphocyte transformation testing. It was originally developed for the diagnosis of occupational allergies at Astra Pharmaceuticals (now AstraZeneca) but is now mainly used to measure lymphocyte reactivity to metals (a Type IV cell-mediated reaction). For testing, whole blood needs to be drawn into tubes containing sodium citrate (an anti-coagulant). 

Inflammation activated by metal hypersensitivity may be one of the causes of ill health in patients. MELISA can identify if metals are causing an immune reaction, which may affect health. Most relevant results are obtained when testing is based on current exposure to metals found in fillings, crowns, orthopedic devices, pacemakers, Essure, occupational exposure etc. Studies show that if metal allergy is found, many symptoms will improve or disappear if exposure to relevant metals is reduced.

Orthopedic and general surgery; dentistry; occupational medicine and environmental health, among others.

Metals are found in body implants such as hip joints, knee prosthesis, screws, pacemakers, silicone breast implants, cochlear implants and dental implants. In most patients, these implants are biocompatible. However, in sensitive patients, the implants may induce side-effects such as pain, dermatitis, cutaneous swelling, impaired wound healing and implant loosening. Excessive fatigue can be due to chronic inflammation due to metal ions released from implants.

Metals are potential allergens. The binding of metal ions to proteins can alter the protein activity and surface structure of these enzymes, thereby inducing local or systemic symptoms. In contrast to a Type I allergy, which is mediated by IgE antibodies, a Type IV allergic reaction is mediated by T lymphocytes that have had prior contact to a given allergen (memory lymphocytes). Following renewed contact with the sensitising allergen, these memory lymphocytes respond by enlarging (lymphoblast transformation) and dividing (proliferation). The newly formed cells (effector cells) together with their secreted cytokines mediate the resulting inflammatory reaction.

Metal allergy is traditionally diagnosed by patch testing, but this can be problematic when testing irritative substances such as mercury, or substances with large particles like titanium dioxide.

Studies show that lymphocyte transformation tests are better suited for diagnosing possible metal sensitivity than traditional patch testing. Implant-related hypersensitivity reactions are mediated by sensitized T cells and the relationship between skin hypersensitivity and systemic hypersensitivity is ill defined. Lack of standardization in patch testing may also contribute to reduced reliability.

Using MELISA avoids many of the issues surrounding patch testing.  

Laboratories need a license to be allowed to perform MELISA testing. All licensed MELISA laboratories receive access to our contact network and comprehensive marketing support; from ready-made marketing materials to exposure through our website melisa.org and through lectures and international conferences.

Certified laboratories may perform the MELISA test under a license agreement. The

MELISA test is protected by trademark. The laboratory will need a license to handle beta radiation (3H thymidine). Equipment needed for testing include cytocentrifuge, CO2 incubator, Betacounter and cell harvester.

Lab technicians performing MELISA testing should have experience in working with primary cell cultures.

Blood in citrate tubes must arrive at the laboratory ideally within 24 hours after the blood has been drawn (maximally within 48 hours). White blood cells (lymphocytes) are isolated and tested against allergens chosen accordingly to the patient’s anamnesis and exposure to metals. The blood is incubated for five days and the lymphocyte reaction is measured in two ways: one based on the uptake of radioisotopes by dividing lymphocytes; the other by microscopic evaluation. The level of reactivity is measured as a Stimulation Index (SI). A value over 3 indicates a positive reaction to a given allergen. The results are available in ten days.