MELISA
Encyclopedia
A MELISA test is a blood test
that detects Type-IV allergy
to metal
s, chemicals, environmental toxins and mold
s from one single blood sample
. It can also identify active Lyme disease
(Lyme Borreliosis). The test does not measure toxicity
-that is to say, it will not measure the amounts of a harmful substance in the patient's blood. It measures if the patient is allergic to it.
Two articles have concluded that the MELISA test is not useful for diagnosis since a large number of false positive results will be obtained.
and is often tested using an ELISA
test, a Type-IV allergic reaction is mediated by T-lymphocytes (or memory lymphocytes) that have had prior contact with a given allergen
. In genetically predisposed individuals, an ongoing everyday exposure to allergens can induce the Type-IV hypersensitivity with a resulting allergic reaction.
The test procedure is a cell culture and requires live memory lymphocytes. Lymphocytes are isolated and cultured in an incubator for five days. A portion of the blood is kept intact (unexposed to allergens) to serve as a negative control. A second portion is exposed to a universal allergen, such as Pokeweed
, to serve as a positive control. Finally, the third portion of the blood is exposed to the suspected allergen in several different concentrations, to ensure that the conditions in vitro are as similar as possible to the ones in vivo.
As an example, if a patient has a suspected allergy to dental amalgams
, then the allergens tested for will be the metals most commonly used in dental amalgams, such as mercury
, silver
, tin
, copper
and so on. If a patient has a suspected contact allergy to nickel then the test can be used to test for nickel allergy. This is especially useful in individuals who have clinical symptoms (contact dermatitis) but a negative patch test. The lymphocyte reaction to such an allergen is measured by two separate technologies: one based on the uptake of a radioactive isotope
by dividing lymphocytes (proliferation); the other by classical microscopy evaluation (transformation). The level of reactivity is measured as a Stimulation Index (SI), against the naïve lymphocytes from the unexposed sample (negative control). Viability and reactivity is determined by cell count as well as reaction to the positive control.
and environmental health. It has been used to screen workers exposed to metals, chemicals or other allergens in their workplace. This is what the test was developed for originally, at the Astra (now Astra-Zeneca) laboratories in Stockholm
, Sweden
. In the U.S., a similar technique (LTT) is routinely used to screen for Beryllium
allergy in asymptomatic workers exposed to Beryllium dust. Other occupations that use sensitivity testing include construction work, mining
, electrical work, rubber/wood/ paper/textile industry work, dentistry
, hairdressing, and painting. The MELISA test is used to screen, diagnose and monitor the immune response of susceptible or affected individuals.
to test for allergy to dental restorative materials, braces and prostheses.
and multiple sclerosis
. The authors hypothesize that if the immune system is constantly staging an allergic reaction to a metal present in the body, this will alert the HPA axis inducing fatigue-like symptoms. A study of 930 fatigue patients showed 62% testing MELISA-positive to metal allergy. Of those who removed the offending metals, 76% improved, but there was no placebo control. Metal allergy is not recognized by scientists as an accepted cause of chronic fatigue syndrome
or multiple sclerosis
.
Another study used 34 patients to test the sensitivity and specificity if the MELISA test, and concluded that it is not useful for diagnosis of contact allergy to the metals gold, palladium and nickel, since a large number of false-positive results will be obtained.
However, according to the MELISA Foundation the studies are flawed, mainly due to the incorrect selection of patients included as well as the use of patch test as a gold standard for the measurement of metal allergy. The clinical relevance of the test has been shown by the decrease of patient-reported metal-specific responses following the removal of the allergy-causing metals (however the trial did not have a placebo control).
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
that detects Type-IV allergy
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
to metal
Metal
A metal , is an element, compound, or alloy that is a good conductor of both electricity and heat. Metals are usually malleable and shiny, that is they reflect most of incident light...
s, chemicals, environmental toxins and mold
Mold
Molds are fungi that grow in the form of multicellular filaments called hyphae. Molds are not considered to be microbes but microscopic fungi that grow as single cells called yeasts...
s from one single blood sample
Blood Sample
Blood Sample is the 10th studio album by the Finnish avant-garde progressive metal band Waltari.-Track listing:# "Helsinki" - 5:53# "Not Enough" - 3:35# "Too Much Emptiness" - 2:30# "Never" - 4:01# "New York" - 3:48# "I'm in Pain" - 4:38...
. It can also identify active Lyme disease
Lyme disease
Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...
(Lyme Borreliosis). The test does not measure toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
-that is to say, it will not measure the amounts of a harmful substance in the patient's blood. It measures if the patient is allergic to it.
Two articles have concluded that the MELISA test is not useful for diagnosis since a large number of false positive results will be obtained.
How the MELISA test works
A MELISA test measures a so-called Type-IV delayed hypersensitivity reaction. In contrast to a Type-I allergy, which is mediated by IgE antibodiesAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
and is often tested using an ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
test, a Type-IV allergic reaction is mediated by T-lymphocytes (or memory lymphocytes) that have had prior contact with a given allergen
Allergen
An allergen is any substance that can cause an allergy. In technical terms, an allergen is a non-parasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals....
. In genetically predisposed individuals, an ongoing everyday exposure to allergens can induce the Type-IV hypersensitivity with a resulting allergic reaction.
The test procedure is a cell culture and requires live memory lymphocytes. Lymphocytes are isolated and cultured in an incubator for five days. A portion of the blood is kept intact (unexposed to allergens) to serve as a negative control. A second portion is exposed to a universal allergen, such as Pokeweed
Pokeweed
The pokeweeds, also known as pokebush, pokeberry, pokeroot, poke sallet, polk salad, polk salat, polk sallet, inkberry or ombú, comprise the genus Phytolacca, perennial plants native to North America, South America, East Asia and New Zealand...
, to serve as a positive control. Finally, the third portion of the blood is exposed to the suspected allergen in several different concentrations, to ensure that the conditions in vitro are as similar as possible to the ones in vivo.
As an example, if a patient has a suspected allergy to dental amalgams
Amalgam (dentistry)
Amalgam is an alloy containing mercury. The term is commonly used for the amalgam employed as material for dental fillings, which consists of mercury , silver , tin , copper , and other trace metals...
, then the allergens tested for will be the metals most commonly used in dental amalgams, such as mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
, silver
Silver
Silver is a metallic chemical element with the chemical symbol Ag and atomic number 47. A soft, white, lustrous transition metal, it has the highest electrical conductivity of any element and the highest thermal conductivity of any metal...
, tin
Tin
Tin is a chemical element with the symbol Sn and atomic number 50. It is a main group metal in group 14 of the periodic table. Tin shows chemical similarity to both neighboring group 14 elements, germanium and lead and has two possible oxidation states, +2 and the slightly more stable +4...
, copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
and so on. If a patient has a suspected contact allergy to nickel then the test can be used to test for nickel allergy. This is especially useful in individuals who have clinical symptoms (contact dermatitis) but a negative patch test. The lymphocyte reaction to such an allergen is measured by two separate technologies: one based on the uptake of a radioactive isotope
Isotope
Isotopes are variants of atoms of a particular chemical element, which have differing numbers of neutrons. Atoms of a particular element by definition must contain the same number of protons but may have a distinct number of neutrons which differs from atom to atom, without changing the designation...
by dividing lymphocytes (proliferation); the other by classical microscopy evaluation (transformation). The level of reactivity is measured as a Stimulation Index (SI), against the naïve lymphocytes from the unexposed sample (negative control). Viability and reactivity is determined by cell count as well as reaction to the positive control.
Occupational medicine
The MELISA test is used in occupational medicineOccupational safety and health
Occupational safety and health is a cross-disciplinary area concerned with protecting the safety, health and welfare of people engaged in work or employment. The goal of all occupational safety and health programs is to foster a safe work environment...
and environmental health. It has been used to screen workers exposed to metals, chemicals or other allergens in their workplace. This is what the test was developed for originally, at the Astra (now Astra-Zeneca) laboratories in Stockholm
Stockholm
Stockholm is the capital and the largest city of Sweden and constitutes the most populated urban area in Scandinavia. Stockholm is the most populous city in Sweden, with a population of 851,155 in the municipality , 1.37 million in the urban area , and around 2.1 million in the metropolitan area...
, Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
. In the U.S., a similar technique (LTT) is routinely used to screen for Beryllium
Beryllium
Beryllium is the chemical element with the symbol Be and atomic number 4. It is a divalent element which occurs naturally only in combination with other elements in minerals. Notable gemstones which contain beryllium include beryl and chrysoberyl...
allergy in asymptomatic workers exposed to Beryllium dust. Other occupations that use sensitivity testing include construction work, mining
Mining
Mining is the extraction of valuable minerals or other geological materials from the earth, from an ore body, vein or seam. The term also includes the removal of soil. Materials recovered by mining include base metals, precious metals, iron, uranium, coal, diamonds, limestone, oil shale, rock...
, electrical work, rubber/wood/ paper/textile industry work, dentistry
Dentistry
Dentistry is the branch of medicine that is involved in the study, diagnosis, prevention, and treatment of diseases, disorders and conditions of the oral cavity, maxillofacial area and the adjacent and associated structures and their impact on the human body. Dentistry is widely considered...
, hairdressing, and painting. The MELISA test is used to screen, diagnose and monitor the immune response of susceptible or affected individuals.
Dentistry
In Europe, the test is commonly used in dentistryDentistry
Dentistry is the branch of medicine that is involved in the study, diagnosis, prevention, and treatment of diseases, disorders and conditions of the oral cavity, maxillofacial area and the adjacent and associated structures and their impact on the human body. Dentistry is widely considered...
to test for allergy to dental restorative materials, braces and prostheses.
Chronic diseases
The test is also used to determine whether metal allergy is a factor behind chronic diseases such as chronic fatigue syndromeChronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...
and multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
. The authors hypothesize that if the immune system is constantly staging an allergic reaction to a metal present in the body, this will alert the HPA axis inducing fatigue-like symptoms. A study of 930 fatigue patients showed 62% testing MELISA-positive to metal allergy. Of those who removed the offending metals, 76% improved, but there was no placebo control. Metal allergy is not recognized by scientists as an accepted cause of chronic fatigue syndrome
Chronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...
or multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
.
Validity
To test whether patients with symptoms attributed to dental amalgam differed from healthy controls, a study compared 23 amalgam patients, 30 healthy blood donors with amalgam and 10 healthy subjects without amalgam using MELISA and other tests. The researchers found that a high frequency of positive results was obtained among healthy subjects with or without dental amalgam, and concluded that the test cannot be used as an objective test for mercury allergy.Another study used 34 patients to test the sensitivity and specificity if the MELISA test, and concluded that it is not useful for diagnosis of contact allergy to the metals gold, palladium and nickel, since a large number of false-positive results will be obtained.
However, according to the MELISA Foundation the studies are flawed, mainly due to the incorrect selection of patients included as well as the use of patch test as a gold standard for the measurement of metal allergy. The clinical relevance of the test has been shown by the decrease of patient-reported metal-specific responses following the removal of the allergy-causing metals (however the trial did not have a placebo control).