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Mast Cells - Normal Role, Allergies, Anaphylaxis, MCAS and Mastocytosis.

Find out all about mast cells, their usual role in fighting infections and how they can cause allergies and anaphylaxis when things go wrong. Also, find out about the mast cell diseases MCAS and mastocytosis.

Mast Cells line the tissues of the body exposed from the outside world. They protect us from foreign invaders, including bacteria, viruses, parasites, and venoms. Watch the YouTube video or read on below to find out more.

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Mast Cells: What are they? Where are they? What do they do?


Mast Cells line the tissues exposed to the outside world. They lie under the surface layer of cells in the skin, nasal cavity, stomach, intestines and lungs. Mast cells also surround blood vessels and nerves. They originate from stem cells in the bone marrow and enter the blood as immature cells. They then migrate to the tissues, where they mature into recognisable mast cells. Note that mast cells are distinct from basophils.


An cartoon illustrator drawing of a human body with magnification of tissues of the skin, lung, stomach/intestine, and nasal cavity. The position of mast cells at each of these locations is shown. There's also a ClevaLab Logo.

Each mature mast cell contains hundreds of granules. These granules contain protein and chemical mediators. One role of mast cells is to protect the body from foreign invaders. They protect the body by detecting bacteria, viruses, parasites, venom or physical harm. This detection is via their cell surface receptors. The most well-known mast cell receptor is the IgE antibody receptor, FcERI. These receptors only exist on mast cells and basophils. The IgE antibody circulates through the body at minute levels. This low level is because the majority is bound to the IgE Receptors. Mast cells also have other receptors. They can respond to IgG antibodies and components of bacteria and viruses. Within seconds of receptor binding, they can release their granules.


Examples of mast cell receptors. There's an IgE antibody bound to an IgE Receptor, an IgG antibody bound to an IgG receptor and a virus particle attached to a Toll-like Receptor on the surface of a mast cell. This is a cartoon illustrator drawing. There is also a ClevaLab logo.

The primary mediators released are histamine, tryptase, chymase, carboxypeptidase A and heparin. These act on the surrounding tissues. They dilate blood vessels to slow the blood flow. As well as make the blood vessels more sticky for immune cells. These effects attract immune cells into the tissues. They make the blood vessels leaky, allowing antibodies to enter the tissues. The antibodies and immune cells neutralise and remove the infection or toxin. Once removed, mast cells make anti-inflammatory mediators. These stop further immune cells from entering the tissue. They also promote the rebuilding of tissues and removal of dead cells. The tissue returns to normal, and the mast cell re-granulates to be ready for future infection.


Mast Cells Cause Allergies and Anaphylaxis:


But, with so many granules ready to release at a moments notice, it's easy to imagine how things can go wrong. An allergy is an overreaction of the immune system to the environment. And mast cells can cause many allergies, such as hayfever, asthma, food allergies, drug allergies, insect stings and insect bites. Whether you develop any of these depends on both your genetics and the environment.


Types of Allergies. The discription says Overreaction of the Immune System to the Environment. This is a cartoon illustrator drawing of exmples of types of allergies are around a mast cell at the center. Hayfever, Food Allergies, Insect Stings/Bits, Asthma and Drug Allergies are listed with an image or each. There's also a ClevaLab Logo.

So, genetics alone is not enough. You also need exposure to the allergen via a broken barrier in your skin, intestine, or lungs. When allergens make it into the tissues, they activate the immune system. The activated immune system produces antibodies, including IgE. IgE antibodies bind to the IgE Receptor (IgeRI) on your mast cells and basophils. When you reencounter the antigen, it binds to the IgE on the IgE Receptor. This binding causes degranulation.


Some peoples mast cells will degranulate with less stimulation than is typical. This response can be due to increased amounts of IgE on each mast cell or other genetic differences. The mediators in granules released by mast cells cause classic allergy symptoms. The type of symptoms experienced will depend on the amount of the allergen and where it enters the body. Inhaled allergen will cause sneezing, congestion, airway swelling, itchy eyes, wheezing, and coughing. An eaten allergen causes swelling in the mouth and esophagus, diarrhea and vomiting. An allergen in contact with the skin causes redness, swelling, and itching. Also, inhaled and ingested allergens can cause dizziness from low blood pressure. Low blood pressure is caused by plasma moving into the tissues and blood vessel dilation.


Classic Allergy Symptoms. This is a cartoon illustrator drawing of a body idicating the syptoms caused by different routes of allergen entry. Inhaled, Eaten and Skin contact. There's also a ClevaLab logo.

Food allergens can sometimes enter the blood via a leaky gut. Allergens circulating in the blood will cause hives or anaphylactic shock. Anaphylactic shock is when blood pressure becomes so low that there is no longer adequate blood supply to the organs. On top of this, swelling of the upper airway obstructs breathing and further reduces oxygen. Because of this, anaphylaxis is life-threatening and sometimes fatal. The body tries to compensate for low blood pressure by increasing the heart rate. But in extreme instances, this is not enough to prevent loss of oxygen to the brain and heart. As a result, the person will become unconscious and go into cardiac arrest. Giving adrenalin via an EpiPen in the early stages of an attack can reverse these symptoms. Adrenalin relaxes the airways, constricts the blood vessels and increases heart rate. All of which increase blood pressure. Adequate blood pressure will ensure continued oxygen supply to the organs. So, adrenalin in the early stages of anaphylaxis is life-saving.


Mast Cell Activation Disorders: Mast Cell Activation Syndrome and Systemic Mastocytosis


In some people, mast cells have DNA mutations. These cause them to be more reactive to known or unknown triggers. These mutations can be inherited or acquired over time. This over-reactivity of mast cells is a feature of Mast Cell Activation Disorders (MCAD). Examples of these are Mast Cell Activation Syndrome (MCAS) and Systemic Mastocytosis.


Mast Cell Activation Syndrome


MCAS is present in up to 17% of people, which is very surprising! Unfortunately, this fact is not well known to GPs or even specialists. So, people can go undiagnosed for decades. Symptoms can affect many organ systems. There can be low blood pressure, palpitations, fast heartbeat and near fainting. Flushing, hives and itching of the skin. Pain in the joints, osteoporosis/osteopenia, and muscle weakness. Stomach reflux, abdominal pain, bloating, alternating diarrhea/constipation, nausea and vomiting. Nasal congestion, shortness of breath, localised swelling of the mouth/lips. Headache, fatigue, numbness or tingling in the hands and feet, brain fog and memory loss. These symptoms are like those experienced during anaphylactic shock.


Mast Cell Activation Syndrome (MCAS) Symptoms. This is a cartoon illustrator drawing of a human body with the main symptoms listed. There are main headings Cardiovascular, Gastrointestinal, Musculoskeletal, Skin, Respiratory and Nurological. There is also a ClevaLab logo.
This image illustrates some of the most common symptoms. However, the uterus can also be affected.

Some people with MCAS also can go into anaphylactic shock when triggered. The symptoms experienced are due to the release of mast cell mediators. Histamine, tryptase, leukotrienes, prostaglandins and many other mediators. The symptoms tend to flare up and calm down in response to triggers. Triggers can include food, fragrances, infections, hormones, exercise, temperature changes and some medications.


MCAS gets diagnosed when at least two organ systems are affected. There is also an increase in blood tryptase levels above normal when experiencing symptoms. And finally, if there is a response to treatment. Mast cells release many mediators. So treatment focuses on preventing mast cell degranulation and blocking the mediators' actions. The standard treatment includes avoidance of triggers. And also antihistamines, mast cell stabilisers, prostaglandin and leukotriene inhibitors. Some people will experience more severe reactions, such as anaphylactic shock. These patients can receive anti-IgE therapy and carry an EpiPen.


Mast Cell Activation Syndrome (MCAS) Treatment. This is a cartoon illustrator drawing of a mast cell and the different types of treatments. First is to avoid triggers and the drug used for each mediator is listed. Aniti-histamines for histamine. NSAIDs (ibuprofen/Asprin) for Prostaglandins. Montelukast for Leukotriens. And Mast Cell Stabilisers to prevent degranulation. There is also a ClevaLab Logo.

The reason people develop MCAS is not known. But, it could be due to a genetic predisposition to accumulate mast cell mutations. These mutations make the mast cells more reactive to triggers than regular people. There is an association between families. But the specific causative inherited gene/s are unknown. There is also the idea that autoantibodies play a role. Autoantibodies are antibodies that recognise self-antigens. These could be activating mast cells.


Systemic Mastocytosis


Systemic Mastocytosis is a mast cell cancer. The symptoms and triggers are identical to MCAS. But, there are more mast cells throughout the body with Mastocytosis. More mast cells mean that there is a higher risk of anaphylaxis. The increased number of mast cells is due to a clonal growth of mast cells from a mutated cell in the bone marrow. Because of this, the mast cell clones can spread through the whole body. As a result, there can be an increase in mast cells in many organs.


Systemic Mastocytosis is a mast cell cancer. This is a cartoon illustrator drawing of a human body with organs showing mutated stem cells in the bone marrow. These mutated stem cells spread throughout the body and cause an increase in mast cell numbers in many organs. There is also a ClevaLab logo.

Diagnosis of Mastocytosis is by several factors. One is having a blood tryptase greater than 20 ng/mL. A high level of plasma tryptase indicates more mast cells than usual in the body. Second, a bone marrow biopsy should show that immature mast cells are present in groups of more than 15. These mast cells are likely to have a spindle shape. Finally, more than 80% of patients have a mast cell SCF Receptor mutation (KITD816V). This mutation makes this receptor always active. Yet, this mutation is not the underlying cause of the disease. So, the mechanism for developing Mastocytosis remains unknown.


Systemic Mastocytosis Diagnosis. This is a cartoon illustrator drawing of the 3 main ways systemic mastocytosis is diagnosed. 1. Blood typtase >20 ng/mL is illistated by a blood tube. 2. Bone Marrow biopsy with >15 mast cells illustrated with a bone and needle. 3. >80% mast cell SCF Receptor Mutation KITD816V illustrated with a picture of an always active SCF Receptor. There is also a ClevaLab logo.

The treatment is the same as MCAS. The aim is to control the symptoms, but as there is a higher risk of anaphylaxis, patients will carry an Epipen. There are also newer drugs for patients with advanced Mastocytosis. These drugs, such as Midostaurin, target the SCF receptor to decrease its activity. As a result, they help lessen symptoms in these patients.


Histamine Intolerance


Many people with MCAD experience food allergies or intolerances. The symptoms experienced are very like those due to histamine intolerance. So, it's essential to know the difference between these two disorders. Histamine intolerance is a sensitivity to histamine containing foods. It occurs in around 1% of people. Usually, histamine in food gets broken down by enzymes in the gut. But, if these enzymes don't work, the histamine from food can accumulate. As a result, histamine causes symptoms like those in MCAD. The leading cause seems to be a deficiency in the DAO enzyme needed to break down histamine. Either due to low levels or a mutation decreasing DAO activity.


Several factors get considered when diagnosing histamine intolerance. First other causes like food allergies or elevated blood tryptase get ruled out. Then blood histamine levels get tested before and after a histamine exclusion diet. If foods high histamine are the cause of symptoms. Then blood histamine levels and symptoms will reduce. The treatment avoids foods high in histamines, such as red wine, beer, canned fish, and fermented sausages. With histamine intolerance, foods alone are the trigger. In comparison, MCAD can have many other triggers. There's no mast cell involvement in histamine intolerance.


Vector Graphic. Histamine Intolerance is a non-allergic food hypersensitivity. An infographic showing that histamine containing foods are eaten. A lack of Diamine Oxidase (DAO) in the intestine, that usually breaks down histamine, causes histamine to accumulate. Increased histamine causes a whole array of symptoms that are listed. The treatment is a low histamine diet. The process of diagnosis is also listed. A ClevaLab logo is in the corner.


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