ISAC: Molecular Allergy Panel

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A brand new method that takes allergy diagnosis to a far superior level.

In Molecular Allergology, sensitization to specific allergen components is measured, which gives the patient’s specific IgE profile in detail. In this way, symptoms due to cross-reaction are explained and help to assess risks in the management of the patient.

ISAC on the other hand is enables the simultaneous detection of 112 allergen components from 48 different main allergen sources. While shedding light on the true sensitization profile of susceptible patients, under favour of cross-reacting proteins,

ISAC can provide information on hundreds of allergenic components in addition to the 48 main allergen sources from which the proteins are derived.

ISAC: Moleküler Alerji Paneli - 14.05.2018 - BİLİMSEL BÜLTENLER - Biruni Laboratuvarı - 0850 241 77 88

ISAC: Molecular Allergy Panel – 14.05.2018 – SCIENTIFIC BULLETINS – Biruni Laboratory – 0850 241 77 88

Allergy is an overreaction of the body to a normally harmless substance and means “different reaction” in ancient Greek. Allergens are usually protein or glycoprotein, rarely polysaccharide macromolecules, triggering the IgE antibody response in humans.

In recent years; Due to the increasing frequency of allergic diseases, the diagnostic approach gains great importance. In the diagnosis of allergic diseases, as in all diseases, the first step is to take a good history, in which the patient’s symptoms are questioned in detail, and to perform a systemic examination, especially in search of clinical signs of allergic diseases. It is extremely important to request appropriate laboratory tests and their clinical interpretation after the history and physical examination.

Allergies are a huge health and socioeconomic burden worldwide, especially in industrialized countries. More than 40% of the population in Europe still suffers from at least one allergy. Approximately 70% of these allergic patients are polysensitized. Children are often affected by atopic dermatitis, allergic rhinitis and allergic asthma. High-accuracy in vitro diagnoses that complement conventional diagnoses; essential for optimal patient management and effective treatment. Multiplex systems streamline treatment procedures by presenting a comprehensive and detailed patient profile in a single test.

Specific IgE antibodies appear in human serum and plasma as a result of sensitization to a specific allergen. Measurement of circulating IgE antibodies provides an objective assessment of sensitivity to an allergen. In general, low IgE antibody levels indicate a low probability of clinical disease, while high antibody levels to the allergen correlate with clinical disease.

Clinical Value of Quantitative Test

  • An increase in IgE antibodies, sensitization can be detected at an early stage before clinical symptoms occur.
  • It helps in understanding the progression of allergic disease.
  • It helps explain the burden of the allergen.
  • It allows the determination of the appropriate treatment for the management of the disease.

ImmunoCAP Major Allergens and ImmunoCAP Components

The diagnosis of allergy is based on the patient’s detailed case history, clinical observations, and the results of the Specific IgE test. Using ImmunoCAP Allergens or ImmunoCAP Allergen Components to detect the presence of IgE antibodies provides the ability to detect major allergens or allergen subcomponents to aid in reliable diagnosis of suspected allergy patient.

Knowing the specific IgE antibody levels provides guidance below on:

  • Determining the appropriate individual treatment method for each patient
  • Reducing exposure to the target allergen
  • Follow-up of the development of tolerance (food allergy, specific immunotherapy)
  • Facilitate optimized individual medical treatment plans (time and dose)

Clinical Value of ImmunoCAP Major Allergens

The results from the ImmunoCAP allergy test are used to detect the specific allergen causing the allergic reaction and to eliminate the allergens that are negative. The results may also be helpful in monitoring specific IgE levels of antibodies over time. An increase in IgE antibodies can be detected at early diagnosis, indicating sensitization before clinical symptoms develop and helping to identify patients at risk for the below on:

  • Allergy state of affairs – Transform of skin symptoms to respiratory symptoms
  • Transform of mild symptoms to severe symptoms
  • Chronicity – Transform of recurring symptoms to persistent symptoms

Clinical Value of ImmunoCAP Allergen Components

Molecular Allergology is the state-of-the-art approach to allergy diagnosis. The single allergen components identified here are used for the detection of specific IgEs based on molecular protein, rather than the traditionally used allergen extracts (Figure 1).

Individual allergen components are highly purified proteins isolated directly from the allergen source or produced recombinantly. The sensitivities developed against these components are measured with separate individual tests to determine which component the patient is sensitive to at the sharp molecular level. This provides a higher level of standardization and differential diagnosis than tests based on allergen extracts. Molecular Allergology systems are a powerful diagnostic tool that facilitates risk assessment and treatment decisions, as they can identify the sensitive trigger of allergy.

ISAC: Moleküler Alerji Paneli - 14.05.2018 - BİLİMSEL BÜLTENLER - Biruni Laboratuvarı - 0850 241 77 88

Figure 1. Specific allergen components from a basic allergen source.

What can allergen components tell us?

Allergen components are proteins that have structural similarity and are grouped under different protein families. The reason for the sensitivity developed against these components, which are found in different amounts in the sources and have different stability is due to their common group characteristics. Depending on the properties of these proteins, the sensitization developed by the patient produces different results. Some allergen components are specific and some are cross-reactive.

What Other Contribution Does Molecular Allergology Provide?

With Molecular Allergology, specific allergen components can be produced from a basic allergen source for advanced diagnosis. Sensitization to these components is measured individually in a separate test and at a precise molecular level it is determined which component the patient is sensitive to. This information provides the basis for the highly sensitive diagnosis of allergy. In Molecular Allergology, extract-based tests are used together with component-specific analyses.

While the extract gives the answer to which allergen source the patient is sensitizing to, the allergen components provide vital information about risk, specificity and cross-reaction.

1) Determines the risk of clinical reaction

Molecular Allergology draws conclusions on the risk associated with sensitization. Sensitization to stable allergen components can elicit local as well as systemic reactions, while sensitization to unstable components is mainly associated with local reactions.ISAC: Moleküler Alerji Paneli - 14.05.2018 - BİLİMSEL BÜLTENLER - Biruni Laboratuvarı - 0850 241 77 88

Şekil 2. Risk levels relevant with common allergen proteins

Specific components – provide unique clues to reveal sources of allergies.

Each allergen source typically contains both specific and cross-reactive allergen components. Specific allergen components are almost uniquely related to their source and are only present in small amounts in a limited number of closely related species. Each allergen source may contain one or more specific allergen components. Sensitization to any of these indicates a true sensitization in the person; this means that the relevant allergen source is the primary cause of clinical symptoms.

2) Explains symptoms due to cross-reaction

Symptoms elicited by cross-reacting antibodies can be distinguished from those caused by true sensitization, which is important for patient management and appropriate avoidance advice. Where only cross-reaction sensitization is detected, it is necessary to find the primary sensitizer.

Identification of cross-reactive components

It is important to identify the exact trigger of the allergy before starting treatment. However, patients; Cross-reactivity of allergens is common in skin tests and clinical tests such as extract-based antibody tests. Analysis of allergen sources and components of each of the most important pan-allergens allows rapid and accurate identification of the exact triggers of allergy symptoms.

The cross-reaction may be exemplified by birch pollen-related food allergy, a syndrome that affects many birch pollen allergy sufferers. The molecular reason underlying the cross-reaction is that patients with birch pollen allergy have specific IgE antibodies specific to the Bet v 1 component. Bet v 1 has structural similarity to related proteins in many foods, such as soy and peanuts. In this way, the patient’s IgE antibodies to Bet v 1 birch cross-react with these related proteins in soy or peanut.

ISAC: Moleküler Alerji Paneli - 14.05.2018 - BİLİMSEL BÜLTENLER - Biruni Laboratuvarı - 0850 241 77 88

Figure 3: PR-10, Protein- is sensitive to heat and digestion. Cooked foods are often tolerated. It is mostly associated with local symptoms such as OAS. It is related with allergic reactions to pollen, fruits and vegetables.

3) Selection of Appropriate Therapy – Contributes to identifying the right patients for Specific Immunotherapy (SIT).

Determination of sensitization to specific allergen components is necessary for successful Specific Immunotherapy. In the light of these findings, the outcome of the treatment to be applied in patients who develop a true sensitization against the component extracted from the relevant allergen source will be positive. SITs are most likely to be successful when the patient is primarily sensitized to the main components of the allergen extracts. Only molecular allergy diagnoses can offer such in-depth information. The most appropriate treatment can then be selected and patients are relieved of the stress of avoiding unnecessary allergens or ineffective SITs.

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Figure 4 : Recombinant allergen-based diagnostic tests and specific immunotherapy specific to birch and meadow grass allergen

Protein Stability and Amount

Food allergen components show different stability to heating and digestion, and their content in the allergen source may vary. Both stability and quantity are reflected by the protein family to which the component belongs. Therefore, it is possible to assess the risk associated with sensitizations by knowing the patient’s sensitization profile and to which family the identified components belong.

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Figure 5 : Immunoglobulin E (IgE) levels of allergen molecules based on structural similarity in an allergen family.

a. 2S albumıns (fındık, bakliyat ve tohumlarda stabil depolama proteinleri) arasında değişken, sınırlı çapraz reaktivite.

b. Bet v 1-PR-10 variable cross-reactivity among homologous food allergens.

c. High cross-reactivity (in pollen, latex and foods) due to the strongly preserved and similar structure of the Profilins

For example, in egg allergy, Gal d1 (ovomucoid) is the main allergen and is used as an indicator of allergic reaction severity. Sensitizations to the heat-sensitive components Gal d2 (ovalbumin), Gal d3 (conalbumin), and Gal d4 (lysozyme) are associated with symptoms that occur only with consumption of raw or lightly cooked eggs. Ovalbumin is used in vaccines and lysozyme is used as a preservative, so patients sensitive to these ingredients may have a reaction to drugs or food products containing the relevant ingredient. Similarly, the reaction to Bos d8 (casein) indicates a strong allergy to milk and dairy products. Casein is often used as an additive, so casein sensitivities can cause sensitivities to many different foods, such as chocolate or potato chips. Bos d (lactoferrin), Bosd4, Bos d5 and Bos d6 components are heat sensitive and sensitivities to these components are mainly associated with reactions to fresh milk. Antibodies to Bos d6 (bovine serum albumin) can also cause a reaction to beef.

ISAC: Moleküler Alerji Paneli - 14.05.2018 - BİLİMSEL BÜLTENLER - Biruni Laboratuvarı - 0850 241 77 88

Figure 6 : Serological tests for the diagnosis of allergies

ImmunoCAP ISAC (Immuno Solid-phaseAllergenChip)

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ISAC: Moleküler Alerji Paneli - 14.05.2018 - BİLİMSEL BÜLTENLER - Biruni Laboratuvarı - 0850 241 77 88

Detection of IgE antibodies in serum plays an important role in the diagnosis of type I allergies. The currently used extract-based method of specific IgE antibodies, ImmunoCAP-FEIA, is the gold standard for allergy diagnosis. However, while this test only allows the simultaneous determination of a limited number of allergens, Immuno CAP ISAC enables the simultaneous detection of 112 allergen components from 48 different main allergen sources. This system is array-based, biochip technology and is the most advanced in vitro diagnostic test for the measurement of specific IgE antibodies for allergen components. The ISAC test facilitates the identification of a comprehensive and specific IgE antibody profile.

ImmunoCAP ISAC is a semi-quantitative test and results report specific IgE antibody levels in ISAC Standard Units (ISU) within the 0.3 – 100 ISU-E measuring range.

ISAC Advantages:

Simultaneous analysis of 112 allergenic proteins allows us to fully and quickly identify the allergens causing the patient’s clinical condition from a single blood sample. The very wide range of allergenic protein studies makes it possible to highlight unexpected sensitizations and/or rule out others. As a result, the analysis allows to obtain an individual sensitization profile with improvement in diagnosis, leading to an individualized treatment. While all this helps improve the patient’s quality of life, the economic cost of analysis is much less than analyzing individual specific IgEs. Most allergic patients test positive to numerous allergens, and the true cause of symptoms may not be determined due to an uncertain medical history regarding the role of different allergens and reactions.

ImmunoCAP ISAC in the diagnosis and treatment of these patients;

  • It sheds light on the true sensitization profile of susceptible patients.
  • It presents the potential risk for severe food-related reactions.
  • It determines the IgE antibody profile in patients with inadequate response to treatment.

Under favour of cross-reacting proteins, ImmunoCAP ISAC can provide information on hundreds of allergen components in addition to the 48 main allergen sources from which the proteins are derived. ImmunoCAP ISAC can reveal unexpected sensitivities or help rule out allergy by providing IgE results for a wide array of allergens. As a result, effective and optimized treatment principles for patients can be initiated earlier and the quality of life is increased while ensuring patient health.

Cross-reacting allergen components are more widely distributed and can be shared among a wide range of allergen sources. Due to their high structural similarity, they can cause cross-reactivity of the IgE antibody.

Components from different protein families produce symptoms of varying severity. Thus, molecular profiling can determine whether a patient has a low or high risk of serious systemic reactions such as anaphylactic shock. Patients at risk of life-threatening reactions can then be advised on allergen avoidance and appropriate measures to be taken in an emergency. For example, if a patient is sensitive to allergens in the profilins family, milder symptoms can be expected overall. Patients who are sensitive to allergens belonging to the family of storage proteins have a high risk of life-threatening systemic reactions. In addition, differences in the heat resistance of protein families play an important role in food allergies.

The prevalence of oral allergy syndrome (OAS) is increasing. It is currently reported to affect approximately 2% of the population in primary care practices in the UK. Although it can often be diagnosed by clinical history, the need for confirmatory testing is increasing for patients with typical oral symptoms after eating raw fruits or vegetables, or sometimes raw nuts. The overlap of symptoms between patients with oral allergy syndrome and patients with nut allergy is an area that often requires more precise definition using available tests to inform patient management and stratify risk. Testing multiple recombinant proteins with ISAC is particularly useful in elucidating patients’ reaction to PR-10 and/or profilin proteins (combined low risk of clinical reaction only) or lipid transfer protein or peanut storage proteins (higher risk of severe reaction).

ISAC Indications:

  • Improving diagnosis in polysensitized patients.
  • To prevent diagnostic errors, especially in patients who do not have a clear correlation between the positive results of conventional allergy tests and symptoms.
  • Preventing therapeutic errors that may occur in terms of Allergen Specific Immunotherapy.
  • To evaluate cases with an inconsistent clinical history of allergy and/or inadequate response to treatment.
  • Evaluation of patients with a history of idiopathic anaphylaxis detecting unexpected sensitivities. ISAC ALLERGEN PROTEIN FAMILIES

ImmunoCAP ISAC provides a large amount of allergen-specific IgE antibody information in a single step. Thanks to cross-reacting proteins, ImmunoCAP ISAC can provide information on hundreds of allergen sources in addition to the 48 sources from which the proteins are derived.

Please Click to overview the ISAC Immunocap Cross-Reaction Map

Storage proteins
  • They are heat and digestion resistant proteins, so they also react with the cooking of foods.
  • They cause more severe systemic reactions in addition to OAS.
  • Proteins found in nuts and seeds as source material for the development of new plants.

 

Profilin (1)
  • These proteins are sensitive to heat and digestion. Cooked foods are often tolerated.
  • Although rarely associated with clinical symptoms, it may cause local or even severe reactions in some patients.
  • Profilins are present in all pollen and food plants.

 

PR-10 protein, Bet v 1 homologue(1)
  • Many of the PR-10 proteins are sensitive to heat and digestion. Cooked foods are often tolerated.
  • It is mostly associated with local symptoms such as OAS.
  • It is associated with allergic reactions to pollen, fruits and vegetables.

 

Polcalcin (Calcium-binding proteins) (2)
  • It is a marker that does not take place in plants used as food, that determines cross-reactivity to pollen.

 

LTP (non-specific Lipid Transfer Proteins, nsLTP)(1)
  • They are heat and digestion resistant proteins, so they also react with the cooking of foods.
  • They are usually associated with systemic reactions in addition to OAS (Oral Allergy Syndrome).
  • It is associated with allergic reactions to fruits and vegetables in the regions where peach and its derivatives are grown.

 

CCD (2)
  • It is a marker that determines the sensitivities developed against cross-reactive carbohydrates.
  • Although it is very rare to cause allergic reactions, pollen containing CCD, plants used as food, pests and poisons can cause positive IVD results.

 

Lipocalin (3)
  • They are important allergens that are constantly found in animals.
  • It is a component that shows limited cross-reactivity between animal species.

 

Parvalbumin (3)
  • These proteins are resistant to heat and digestion. They also cause a reaction in cooked foods.
  • They cause more severe systemic reactions in addition to OAS.
  • The main allergen is found in fish and is a marker that determines cross-reactivity between different fish species and amphibians.

 

Serum albumin (3,4)
  • These proteins are very sensitive to heat and digestion.
  • Animals inhabit different biological fluids and regions. eg. cow’s milk, blood, meat and epithelium.
  • They cause cross-reactions between different common mammalian species. For example: Cat-dog and pig

ISAC IMPORTANT ALLERGEN COMPONENTS

Gal d 1, Ovomucoid (egg white / glair) (3)
  • Ovomucoid IgE antibodies are associated with persistent egg allergy and are generally intolerable both raw and cooked.

 

Tropomyosin (3)
  • These proteins are resistant to heat and digestion. They also cause a reaction in cooked foods.
  • They cause more severe systemic reactions in addition to OAS.
  • It is actin-binding proteins in muscle tissues and is a marker that determines cross-reactivity between shellfish, mites and cockroaches.

 

Ara h 1, 2, 3, 6, 8 and 9 (peanut) (3)
  • Intermediate h 1, 2, 3, 6 and 9 (LTP) IgE antibodies cause peanut-induced systemic reactions in addition to OAS.
  • Intermediate h 8 (PR-10) IgE antibodies generally cause milder local symptoms such as OAS. It is often associated with birch-related sensitivities.

 

Gly m 4, 5 and 6 (soy) (3)
  • Patients allergic to soybean often have Gly m 5 and Gly m 6. Gly m 5 & Ara h 1 and Gly m 6 & Ara h 3 IgE antibodies. Cross-reactivity and clinical reactivity may be seen due to IgE of the storage proteins found in these legumes.
  • Gly m 4 (PR-10) IgE antibodies are usually associated with local symptoms such as OAS and arise from birch sensitivity. However, some cases of severe reactions to Gly m 4 have also been reported. eg. during birch pollen season, often combined with exercise and intake of less processed soy beverages.

 

Alt a 1 (Alternaria) (3)
  • Alt a 1 is the main allergen of Alternaria, which is associated with the development of asthma.

 

Tri a 19, Omega-5 gliadin (wheat) (5,6,7)
  • Omega-5 gliadin (Tri a 19) IgE antibodies in adults are associated with reactions triggered by exercise or the use of NSAIDs due to wheat ingestion.
  • Omega-5 gliadin (Tri a 19) IgE antibodies are associated with an increased risk of immediate reactions to wheat in children.

 

ISAC: Moleküler Alerji Paneli - 14.05.2018 - BİLİMSEL BÜLTENLER - Biruni Laboratuvarı - 0850 241 77 88

 

COVID-19 Numerical (Quantitative) IgG Antibody Test

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COVID-19 Numerical (Quantitative) IgG Antibody Test 

What is an Antibody?

  • Antibodies are proteins that help the immune system identify and eliminate threats.
  • After illness or vaccination, our body produces antibodies to protect against infections.

What are the differences between PCR and Antibody tests?

  • The antibody test enables the body to detect the natural immune response against the COVID-19 virus and the immunity level that will arise from the vaccine.
  • The PCR test is a molecular diagnostic test that shows the RNA (genetic material) of the virus. A positive PCR result means that the virus is present at the time the sample is taken.

Which Antibody is looked over for in COVID-19 immunity?

  • Numerical measurement of the IgG immune antibody against the spike protein of the virus is more valuable in evaluating the immune response of the person.
  • The vaccines used aim to create an antibody response against the spike protein.

When should a COVID-19 Quantitative IgG Antibody test be performed?

  • The onset of antibodies is usually detectable 15 days after the onset of the disease.
  • To evaluate the post-vaccine immune response, the dose must use 21 days after the vaccination.

Does the COVID-19 Quantitative IgG Antibody test reliable?

  • IgG antibodies are determined numerically by the chemiluminescent microparticle immunoassay CMIA method, which is a reliable method.
  • The tests performed with this method have a high clinical specificity of 99.60% and a sensitivity of 99.94%.

How Does the COVID-19 Numerical IgG Antibody test done?

  • The antibody test is performed from a blood sample.

When Does the result of the COVID-19 Numerical IgG Antibody test be available?

  • The antibody test results within 24 hours.

How are the results interpreted?

  • Negative for Anti SARS CoV 2 IgG Antibody < 50 AU/mL 
    It is interpreted as positive for Anti SARS CoV 2 IgG Antibody ≥ 50 AU/mL.
  • The antibody test shows whether or to what level our immune system responds to the vaccine or virus.
  • The presence of IgG antibodies in unvaccinated people means that the person has recovered from the disease and possibly has developed immunity.

Why is COVID-19 Numerical IgG Antibody testing important?

  • It may have use to determine the immune response against the COVID-19 vaccine.
  • Immunity levels of people who have been infected can be evaluated.
  • People who have immunity can contribute to the treatment by donating plasma for severe patients in need of antibodies.

Can not IgG antibody occur after vaccination or illness?

  • Antibody responses measured by methods other than rapid tests have a high detection rate if sufficient antibodies are formed.
  • The reason why the result is negative is related to the immune response of the person and antibody response may not occur. It may occur and fall in a short time / may not occur at a sufficient level.

Does getting an infection to protect a person from a new disease?

  • It is not scientifically clear yet whether antibodies against the COVID-19 virus can protect us from a new infection.
  • No antibody level measured after vaccination or after infection can not tell us exactly that how much protection we have against COVID-19.

HORMONE METABOLISM PANEL

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  • Hormonal balance is the key to a healthy life. Hormone Metabolism Panel: It is a test group that examines hormones with different characteristics such as Estrogen, Progesterone, Testosterone, DHEA, Cortisone, Aldosterone, Melatonin and their metabolism products.
  • After the hormones have completed their duties, they go to the liver and enter the process of being removed from the body. At this stage, some problems may occur, metabolism products and toxic substances may accumulate in the body. As a result, some complaints and disease manifestations may occur.
  • Hormone Metabolism Panel test results show whether the hormones in our body are properly excreted after completing their functions. It is an important indicator for a healthy life.
  • When hormones cannot be metabolized as they should be, they may cause the person to face various disease risks as well as acquire a carcinogenic nature.

 

STEROID HORMONE METABOLISM 

HORMONE METABOLISM OF OUR BODY

  • The way in which hormones are metabolized and excreted from the body may change in some cases. For example, our body may secrete too much cortisol to cope with stress, and as a result, the production of sex hormones may decrease.
  • Harmful metabolism products of hormones may occur due to consumption of foods containing excessive fat, lack of vitamins, and unbalanced nutrition. Many factors such as metals, genetic defects of enzymes involved in the formation of metabolic products affect these processes.
  • Whether the hormone metabolism product is toxic or not, whether it accumulates in the body, the level of effect, why it increases or decreases that is understood by the Hormone Metabolism Panel test results.

 

IMPORTANCE OF THE HORMONE METABOLISM PANEL

  • Measuring the blood levels of hormones as well as the metabolism product levels is very important in terms of more comprehensively determining the risks of the person
  • Hormone Metabolism Tests are studied on four different urine samples collected at certain times of the day. In these samples, very low levels of hormone metabolism products, which cannot be detected in the blood and are excreted in the urine, that are also analyzed together with the hormones.
  • The test results also show the cortisol hormone response of your body to against the stress.
  • In addition to hormones, Bisphenol A (BPA) levels are also analyzed. BPA is a chemical compound found in the packaging of food and beverages. It has been proven that BPA, which enters the body through food and beverages, has harmful effects on the function, secretion, transport of hormones.

 

WHEN SHOULD WE CONSIDER TO HAVE DONE TO

THE HORMONE METABOLISM PANEL?

  • If you have a family history of hormone-related cancer such as breast or prostate cancer,
  • Weight gain, insomnia,
  • Insulin resistance, waist circumference thickening, excessive sweet or salty desire to eat,
  • Bone muscle pains,
  • Depression,
  • Excessive hair loss, excessive hair growth, acne,
  • Menstrual irregularities,
  • Night sweats, hot flashes,
  • If there are signs of menopause and hormone therapy will be started,

          The Hormone Metabolism Panel will guide you.

INTRACELLULAR AND EXTRACELLULAR MINERALS AND METALS

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WHY DOES MINERALS IMPORTANT?

→ They take part in many steps of metabolic activities.
→ They enable to provide work of enzymes.
→ It are especially important for the immune system, nervous system, antioxidant capacity, mitochondria function, gut and bone health and hormone balance.

Because of ıt have a pretty common role in metabolism, their deficiencies can cause different complaints.

For example; Recurrent infections, inflammatory diseases, cognitive dysfunctions such as memory, concentration, perception, learning, reasoning, and hormonal disorders can be observed.

Excessive use of one mineral can cause deficiency of others. 

When minerals are overused, they can damage metabolic processes. For example, when zinc added to many supplements and drugs is used excessively, it can reduce the absorption of copper mineral and cause histamine intolerance symptoms (nasal congestion, itching, rash, redness, diarrhea, headache, etc.).

Mineral levels should not be evaluated ıtself.

WHY SHOULD MINERALS AND METALS BE CONSIDERED TOGETHER?

Some metals can inhibit the action of vital minerals. In this case, even if the minerals are within normal limits, they do not bind to the enzymes and the metabolism does not work properly. E.g; It exists between cadmium/zinc, nickel/magnesium, lead/calcium and mercury/selenium. Therefore, along with calcium, zinc, magnesium and selenium, lead, cadmium, nickel and mercury measurements should also be made. It is necessary to detect these interactions in order to correctly evaluate the mineral balance. Therefore, intracellular and extracellular metal mineral analyzes are recommended.

WHY DOES MINERALS IMPORTANT?

Minerals have different roles in metabolism steps. For example, zinc participates in more than 300 reactions for the metabolism to work. In case of deficiency, immune problems, delayed wound healing, growth-development and problems during pregnancy can be seen. In addition, hair loss, diarrhea, eczema, psoriasis, frequent infections, behavioral disorders, delayed wound healing, white spots on nails, appetite and taste disorders can also be seen in zinc deficiency. In childhood zinc deficiency, symptoms of short stature, growth retardation and delayed puberty may occur.

Although red meat, eggs, dairy products, offal, seafood, nuts, almonds, walnuts, seeds, legumes, cereals, flaxseed, wheat bran, fruits and vegetables are consumed regularly, mineral deficiency is still very common. The cause of mineral deficiencies may be insufficient intake with food or other minerals and metals blocking them.

Are minerals important for intestinal permeability?

The healthy functioning of the intestines is necessary for the absorption of all food items, minerals and vitamins. Metals are the most common toxins worldwide that pose serious health threats. Therefore, it should not be absorbed from the intestines. Selenium, magnesium, calcium and zinc are very important in maintaining this delicate balance in the intestines. It has been shown in clinical studies that intestinal permeability increases in deficiencies and decreases when supplemented.

 

Why are intracellular and extracellular evaluations of MINERALS and METAL levels important? 

Almost all of the minerals and metals are found inside the cell. In routine laboratory analyses, extracellular (serum) evaluation is not sufficient. For this reason, studying metals and minerals both in the intracellular and extracellular areas provides the most sensitive evaluation. With various analyzes, we can determine metal and mineral levels with the latest technologies and provide clarification of the individual situation.

 

A New Metabolic Organ: “Intestinal Microbiota”

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Since the moment which we have born there are many microorganisms accompanying us in our body. The human body contains a microbial population, mostly bacteria, including fungi, viruses and protozoa. Bacteria are generally known as disease-causing pathogens. However, humans live in a symbiotic balance with bacteria. It should not be forgotten that we need bacteria and their beneficial effects to stay healthy.

 

Many different microbial populations reside in the human body, mostly bacteria, including fungi, viruses, and protozoa. This population contains 10 times more microbial cells than human cells and 150 times more genes than the human genome. This ecological community formed by commensal, symbiotic and pathogenic microorganisms that share our body is called “microbiota”. “Microbiome” is defined as the total genome of microorganisms living in this environment. (1)

The human microbiota has been colonized in the skin, genitourinary system, respiratory system, and most often in the gastrointestinal tract. The gastrointestinal tract contains the richest microorganism community in our body, due to its surface area of approximately 200m² and rich nutrients for microorganisms. In healthy individuals, the microbiota includes a large number and variety of microorganisms. It begins to form immediately after birth. It varies according to nutrition, genetics, age and geographic region. Bacteria count is 10⁹ ml/saliva in the mouth, 102-4 g/material in the stomach, 10¹¹ g/material in the colon and 10¹² g/material in the stool. The mode of birth, diet, and genetic factors affect the microbiota in infants. Intestinal microbiota may change after treatment applications such as infections and antibiotic use (2)

Dietary content plays an important role in the change of intestinal flora. A diet rich in fiber foods facilitates the proliferation of Firmicutes bacteria such as Eubacterium rectale, Eubacterium halli, Rumicoccus bromii (Picture 1).

 

 

Picture 1: Effect of nutrition on intestinal microbiota (Flint et al.) WK: Wheat-containing food BS: Fiber-containing food EW: Protein-containing food

Intestinal microbiota; It plays a very complex and active role on the physiological, metabolic and immune system in our body. Intestinal bacteria control the necessary metabolic processes by acting as energy carriers or releasing immune-modulating substances. For this reason, the intestinal microbiota is now defined as a new “metabolic organ” (3).

Commensal intestinal bacteria;

•

  • It breaks down indigestible foods and makes them useful for the body.
  • Supports the digestion of complex carbohydrates and fibers.
  • It prevents the reproduction of pathogenic bacteria.
  • Contributes to the production of vitamins B1, B2, B6, B12 and K.
  • Contributes to the detoxification of toxins and wastes.
  • They ferment carbohydrates and proteins taken with food and turn them into short-chain fatty acids such as lactic acid, butyric acid, acetic acid, and gases such as hydrogen and carbon dioxide.
  • Short-chain fatty acids are an energy source for intestinal mucosal cells.
  • Short-chain fatty acids contribute to proper intestinal peristalsis.
  • Butyrate provides a strong anti-inflammatory activity by inactivating Nuclear Factor Kappa (Factor NF-kB) transcription and IL-8 production. It is accepted that Firmicutes bacteria, especially Faecalibacterium prausnitzii, play the most active role in butyrate production. These bacteria make up 5-15% of the intestinal flora. Acute phase reactant proteins such as alpha 1 antitrypsin and calprotectin are responsible for inflammatory irritation in the intestinal mucosa.

A decrease in F. prausnitzii correlates with an increase in the degree of inflammation.

  • Colon epithelial cells in healthy individuals are covered with a protective mucous layer. Bacteria of the genus Verrucomicrobia contribute to immune modulation by promoting mucosal production, especially from Akkermansia muciniphila goblet cells. When the mucosal layer is damaged or mucin production is insufficient, pathogens, pollutants and allergens come into direct contact with the mucosal cells and cause inflammation. (4,5)

DYSBIOSIS

Intestinal microbiota may change due to chronic gastrointestinal diseases as antibiotic use. Disturbance in the intestinal microbiota balance is defined as “dysbiosis”. It has been shown that there is an increase in intestinal permeability, a change in the production of short-chain fatty acids, and a decrease in colonic resistance when the microbiota balance is disturbed. A decrease in Firmicutes strains and an increase in Proteobacteria species such as Salmonella, Shigella, Klebsiella, Proteus, Escherichia coli are associated with various diseases.

Sulfate-consuming bacteria lead to the production of hydrogen sulfide (H2S), paving the way for the development of intestinal diseases. H2S is a toxic metabolic product that damages the intestinal epithelium, resulting in cellular atypia. Bilophilia wadworthii, Desulfomonas pigra and Desulfovibrio piger species are bacteria that play an important role in H2S production. Clostridium species, which are obligate anaerobes, are pathogenic bacteria due to their immune modulatory effects and increasing IL-10 production. Toxin-producing origins of bacteria of the genus Clostridium, in particular, are detected in patients with autistic spectrum, often causing intestinal and extra-intestinal autistic complaints.

Haemophilus and Fusobacteria species, which are known as vepathogens in the respiratory tract mucosa, can also be detected in the intestines. Studies show that these pathogenic strains are associated with chronic inflammatory bowel diseases, colorectal carcinomas and appendicitis. As molecular-genetic studies in stool increase, this relationship will be better defined (6,7).

RELATIONSHIP OF DYSBIOSIS AND CLINICAL SYMPTOMS

Pretty valuable results have been obtained with detailed analyzes of the intestinal microbiota. The ideal organization of the intestinal flora population is one of the main elements of a healthy physiological life. When the intestinal microbiota is defined personally, solutions such as diet regulation according to the presence of increased or decreased origins and the use of appropriate prebiotic probiotics can be applied.

 

1. Obesity and Metabolic Syndrome

In healthy individuals, the Firmicutes/Bacteroidetes ratio usually ranges from 1:1 to 1:3. In overweight people, this ratio varies from 3:1 to 25:1. It has been shown to reach a ratio of 200:1 in some overweight individuals (8 ,9).

Another consequence of obesity is a significant decrease in the amount of Faecalibacterium prausnitzii belonging to the firmicute genus. F.prausnitzii is one of the 3 most common bacteria in the intestinal flora. It produces butyrate. Butyrate supports the development of the intestinal mucosa. Butyric acid salts inhibit the transcription of Factor NF-kB and inhibit the release of additional chemokines and interleukin 8. In obese, hsCRP and interleukin 6 levels are significantly increased, at the same time the amount of F.prausnitzii is decreased. In these patients, when the amount of F.prausnitzii is increased, the mucosa can be protected and inflammatory reactions can be reduced (4).

A. muciniphila species that contribute to the production of mucus produced from goblet cells are also frequently reduced in overweight individuals. Mucus covers the intestinal epithelial cells and forms a barrier that protects them from chemical and mechanical effects. It has been shown that the amount of Akkermansia muciniphila is significantly reduced in people who are fed a high-fat diet. The number of bacteria can be partially increased by adding prebiotics containing oligosaccharides to the diet of these people. In animal experiments, the positive effects of A. muchiniphila supplementation on weight loss, development of mucosal layer and reduction of fasting blood glucose and insulin resistance have been shown. It has been reported that similar results have been obtained in humans (10).

2. Intestinal Inflammation

Irritable bowel syndrome is a common, long-lasting clinical picture that is seen in many people and manifests itself with attacks. Recent studies have shown that the amount of F. prausnitzii is reduced by approximately 30% in people with irritable colon complaints and Crohn’s disease. Considering that F. prausnitzii species play the most important role in the production of butyrate, which has an anti-inflammatory effect, and the inhibitory effect of butyrate on Factor NF-kB and IL-8, this decrease negatively affects the anti-inflammatory effect on the mucosa (4,6)

Campylobacter species are isolated in approximately 70% of children newly diagnosed with Crohn’s disease. For this reason, when Campylobacter species are isolated in the stool, there is a growing debate that administration of probiotics will reduce pathogenic bacteria (11).

Leaky gut syndrome is a clinical pattern suggested to be closely related to the intestinal microbiota. The amounts of A. muchinophilia and F. prausnitzii were decreased in these individuals. Intestinal cells are like bricks lined up next to each other. There are “tight connections” between them, which we can call cement between bricks. Thus, undesirable substances cannot pass out of the intestine (ie inside the body) from here, they remain in the intestine and are excreted from the large intestine. In order for the shape of the intestinal cells and the connection between the cells to be healthy, the cells must be taut, which is when the intestines have enough energy to stay taut. F. prausnitzii species use dietary polysaccharides to form short-chain fatty acids. Energy is also produced from short-chain fatty acids. Just on the outer surface of the intestine, there are immune system cells that examine the substances passing through the intestine. When there is an excessive passage through the gut, these immune system cells become active and initiate a reaction, but this reaction is too small to cause disease.

This is called low-level inflammation. Low-level inflammation does not end as long as intestinal permeability continues, which causes all the body’s energy to be used by immune system cells in a long time. Therefore, sufficient energy cannot go to other organs in need, and some problems begin to occur in these organs. Another bad side of hyperpermeable bowel syndrome is that unwanted substances that enter the body go to the weak tissues of the body and accumulate there, and in the long term, the immune system attacks these tissues, causing autoimmune diseases (12,13).

3. Intestinal Tumors and Intestinal Cancers

In addition to other known carcinogenic effects that acids, especially hydrogen sulphate, increase atypical cell growth, cause mucosal irritation and predispose to colorectal cancer. Sulfate producing bacteria are Desulfomonas piger, Desulfovibrio piger and H2S producing Clostridium species. Pro-prebiotic therapies can be applied when an increase in the number of sulfate-producing bacteria is seen in the stool microbiome analysis.

It has also been shown that intestinal microbiota changes in intestinal tumors. In these individuals, the amount of F. prausnitzii is frequently reduced to an undetectable (13).

4. Arthritis

Bacterial imbalances are detected in the intestinal microbiome of patients with rheumatoid arthritis, paralleling the development and progression of the disease. For example, Prevotella copri is beneficial for the immune and digestive system when it is within physiological limits in the intestinal microflora. However, it has been reported that the amount of Prevotella copri and other prevotella species is significantly increased in patients with rheumatoid arthritis. It is suggested that this situation prevents other beneficial bacteria from reproducing and performing their functions (14).

5. Autism

Genetic factors play a big role in autism. However, many other factors can also cause the development of the disease. Many intestinal diseases accompany clinical complaints including the autistic spectrum. Studies show that the use of antibiotics not only eases intestinal complaints, but also increases other symptoms of autism. It is suggested that intestinal microflora also contributes to brain development through the brain-gut axis. It has been reported that the deterioration of gut biodiversity not only leads to the development of autism, but also increases the severity of symptoms. Toxin-producing Clostridium species are found to be increased in children with autism. More Clostridium species are isolated in children with autism than in the control group with normal neurological development. However, it is not yet fully understood how the excess of Clostridium species plays a role in the onset and development of autism. When toxin-producing strains of Clostridium species are detected in the stools of children with autism, appropriate probiotic use is recommended (7,15).

6. Alzheimer Disease

In a recent study, it was shown that the amount of F. prausnitzii decreased by 100% in the intestinal microflora of Alzheimer’s patients (n=52). In addition, inflammation indicators such as calprotectin and antitrypsin were found to be increased in 87.5% of the stools of these patients. hsCRP values are high in 91% of these patients. These data indicate the presence of a systemic inflammation in the body, and it is suggested that a decrease in the amount of F. prausnitzii may be the cause of this inflammation (16). As a result, with personalized advice and personalized treatment approaches are possible by determining the personal gut microbiota.

References & Sources

  1. Turnbaugh, P.J.; Ley, R.E.; Hamady, M.;Fraser-Liggett,C.M.; Knight, R.; Gordon,J.I. (2007). “The Human Microbiome Project”. Nature 449: 804-81O.
  2. Bull M.J., Plummer N.T.. Part 1: The Human Gut Microbiome in Health and Disease. in: lntegrative Medicine: A Clinician’s Journal 13(6), S. 17-22, 2014
  3. Jandhyala, S. M. et al: Role of the normal gut microbiota. in: World J Gastroenterol 21(29), S.8787-8803,2015
  4. Miquel, S. et al.: Faecalibacterium prausnitzii and human intestinal health. in: Curr Opin Microbiol. 16(3), S. 255-261, 2013
  5. Everard A., et al.: Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. in: PNAS 110(22), S. 9066-9071, 2013
  6. Ramezani, A. et al.: The Gut Microbiome, Kidney Disease, and Targeted lnterventions. in: JASN 25(4), S. 657-670, 2014
  7. Song, Y. et al.: Real-Time PCR Quantitation of Clostridia in Feces of Autistic Children . in: AEM 70, S.6459-6465,2004
  8. The NIH HMP Working Group et al.: The NIH Human Microbiome Project. in: Genome Res. 19, S. 2317-2323, 2009.
  9. Kasai et al. Comparison ofthe gut microbiota composition between obese and non-obese individuals in a Japanese population, as analyzed by terminal restriction fragment length polymorphism and next-generation sequencing BMC Gastroenterology (2015) 15:100 DOI10.1186/sl 2876-015-0330-2
  10. Everard, A. et al.: Cross-Talk between Akkermansia muciniphila and lntestinal Epithelium Controls Diet-lnduced Obesity. in: PNAS 110(22), S. 9066-9071, 2013
  11. Deshpande, N. P. et al.: Comparative genomics of Campylobacter concisus isolates reveals genetic diversity and provides insights into disease association. in: BMC Genomics 14, 585, 2013
  12. Michielan, A. et al.: lntestinal Permeability in lnflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut. in: Mediators of lnflammation, 2015, 628157
  13. Nava G.M. et al.: Abundance and diversity of mucosa-associated hydrogenotrophic microbes in the healthy human colon. in: The iSME Journal 6(1), S. 57-70, 2012
  14. Seher, J. U. et al.: Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. in: elife, 2, e0l 202, 2013
  15. Smith, P.A.: Brain, meet gut. in: Nature 526, S. 312-314, 2015
  16. Leblhuber, F. et al.: Elevated fecal calprotectin in patients with Alzheimer’s dementia indicates leaky gut. J Neural Transm (Vienna) 122(9) S. 1319-1322, 2015
  17. Mandal, S. et al.: Analysis of composition of microbiomes: a novel method for studying microbial composition. in: MEHD 26, S. 27663-27670, 2015

MICROBIOTA

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The human body is contains to a variety of microorganisms, the majority of which are bacteria, including fungi, viruses, and other protozoa. Bacteria and other microorganisms are generally known for their disease-causing effects. However, there bacteria that do not have a disease-causing effect but also bacterias are beneficial for us. We can lead a harmonious, balanced life with these beneficial bacteria. As long as the beneficial bacteria do not disappear and leave their place to harmful, disease-causing bacteria.

The whole community of microorganisms that we share our body with is called Microbiota, the total gene structure of this community and the environment with which it interacts are called Microbiome. The Microbiota we live with contains ten times more microorganisms than human cells and one hundred and fifty times more genes than the human genome.

The human microbiota is located on the skin, reproductive organs, respiratory and most often intestinal tract. Due to its large surface area and rich nutrients for microorganisms, our intestines contain the densest and most diverse microorganism community in our body. The microbiota, which includes a large number and variety of microorganisms in healthy individuals, begins to form naturally after birth. It varies according to nutrition, genetic structure, age and geographic region.

Intestinal microbiota plays a pretty complex and active role on our physiological, metabolic and immune systems. Many chemical reactions by gut bacteria play an important role. In this way, compounds that humans cannot digest on their own are digested by bacteria.

This allows us to benefit from a wider range of foods. The intestinal microbiota is also important for the formation and development of the immune system. The developing immune system learns to distinguish between beneficial and harmful bacteria. While it tolerates beneficial bacteria, it gives a defensive response against disease-causing ones. The ideal structure of the intestinal bacterial flora is one of the main elements of a healthy life. There are indications that the gut microbiota may affect sleep patterns, mood, and some other behaviors. For the reasons listed above, the gut microbiota is now defined as a new ‘metabolic organ’.

 

Beneficial Bowel Bacteria

  • By making the environment acidic, they prevent the proliferation of harmful bacteria causing disease, the formation of inflammation in the intestinal mucosa, the passage of toxic products from the intestines to the blood, and thus the formation of diseases.
  • They help break down and absorb indigestible carbohydrates through the enzymes they produce. Fermented carbohydrates are converted into short-chain fatty acids. These are also used as energy sources. Calcium, magnesium and iron absorption increases. Proper bowel movements are ensured.
  • They contribute to the production and absorption of vitamins B1, B2, B6, B12 and K.
  • They play a role in the early development and lifelong functioning of the immune system by stimulating the lymphatic tissues located near the intestinal mucosa. They enable the immune system to respond only to disease-causing microorganisms.

 

Does the Bowel Microbiota Change?

Bacteria settle in the digestive tract as soon as the baby is born. Bacteria that settle first are recognized by the immune system. Therefore, the bacteria that settle first determine the content of the intestinal bacterial flora that will exist throughout the person’s life. The mode of birth, diet, and genetic factors affect the microbiota in infants. Intestinal microbiota content changes after chronic digestive system diseases, infections and antibiotic use. The change in the balance of healthy and beneficial microorganisms in the intestine in favor of harmful microorganisms and the deterioration of the ideal balance have been associated with many acute and chronic diseases. For this reason, it is important to determine the current status of the person by analyzing the microbiota in the stool.

 

Diseases Related with Impaired Bowel Microbiota

Diseases Associated with Impaired Gut Microbiota

Diabetes, Obesity, Metabolic syndrome

Allergic diseases (Rhinitis, Asthma, Atopic eczema)

Functional bowel diseases (irritable bowel syndrome, infantile colic)

Inflammatory bowel disease, Necrotizing colitis

Autism, Depression, Anxiety disorder

Rheumatoid arthritis, Non-alcoholic liver disease

Colon cancer

 

How to Detect Bowel Microbiota Content?

Just as each person has a different genetic makeup, they may have a different microbiota. The characteristic features of bacteria are encoded in their genes. In this way, it is possible to identify the bacteria that make up the intestinal microbiota by using advanced molecular genetic analyzes. In the stool sample, it is possible to have information about the intestinal microbiota by detecting the bacterial genes with the newly developed DNA sequencing method. For this test, the stool sample must be taken into the sterile container you provide from our laboratory and delivered to our laboratory quickly.

 

The Contribution to Our Health Which Is Knowing the Content of Bowel Microbiota

The key to a healthy and long life is a healthy gut structure. Therefore, there are numerous benefits to knowing the personal gut microbiota content. If harmful microorganisms that can cause disease in the intestine are more intense, the balance of the microbiota is disrupted and the situation we call dysbiosis occurs. After the influence of foreign bacteria in a dysbiotic environment, an uncontrolled inflammation process begins. This can lead to the development of many diseases. In such a case, personalized advice and treatment approaches are possible, and solutions such as diet regulation according to the presence of increased or decreased bacteria, and the use of appropriate probiotics and prebiotics can be suggested.

*Probiotic (Bacterial cells that are beneficial for the intestine and friendly to the human body. These can be found in various foods or given as supplements.)

*Prebiotics (Special nutrients taken to feed beneficial and friendly bacteria and ensure their development)