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Video to understand what is this immunodeficiencies.  

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What is Wiskott-Aldrich Syndrome (Xinyi)

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What is Wiskott-Aldrich Syndrome (Xinyi)

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Osmosis - A Better Way To Learn Wiskott-Aldrich syndrome: Video, Anatomy & Definition | Osmosis

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Osmosis - A Better Way To Learn - Wiskott-Aldrich syndrome: Video, Anatomy & Definition | Osmosis

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Wiskott-Aldrich syndrome Videos, Flashcards, High Yield Notes, & Practice Questions. Learn and reinforce your understanding of Wiskott-Aldrich syndrome. - Osmosis is an efficient, enjoyable, and social way to learn. Sign up for an account today! Don’t study it, Osmose it.

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Symptoms of Wiskott-Aldrich Syndrome (Xinyi)

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Symptoms of Wiskott-Aldrich Syndrome (Xinyi)

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Eczema: It is a skin condition that causes itchy, dry patches of skin.

Immune deficiency: White blood cell that help keep your body healthy do not work as they should or don’t function at all. As a result, your immune system can attack itself and make you ill. This can cause frequent infections, rheumatoid arthritis, vasculitis, anemia, leukemia or lymphoma.

Problems with bleeding (micro-thrombocytopenia): Your blood is not able to clot as it should, or stop excessive bleeding. This happens because you have fewer and smaller blood cells that are responsible for clotting which is the platelets. It can cause bruising, nosebleeds, bloody diarrhea, bleeding under the surface of your skin and a skin rash with tiny red dots (petechiae).

Infants with loss of function Wiskott-Aldrich syndrome may present with:

Eczema

Immune deficiency

Severe thrush

Pneumonia

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What are the symptoms of Wiskott-Aldrich syndrome?

There are three main symptoms of Wiskott-Aldrich syndrome:

Eczema: Eczema is a skin condition that causes itchy, dry patches of skin.

Immune deficiency: White blood cells that help keep your body healthy don't work as they should or don't function at all. As a result, your immune system can attack itself and make you ill. This can cause frequent infections, rheumatoid arthritis, vasculitis, anemia, leukemia or lymphoma.

Problems with bleeding (microthrombocytopenia): Your blood isn't able to clot as it should, or stop excessive bleeding. This happens because you have fewer and smaller blood cells that are responsible for clotting (platelets). It can cause bruising, nosebleeds, bloody diarrhea, bleeding under the surface of your skin (purpura) and a skin rash with tiny red dots (petechiae).

Infants with loss of function Wiskott-Aldrich syndrome may present with:

There may be severe bacterial infections or myelodysplastic syndrome for gain-of-function WAS (congenital neutropenia).

What causes Wiskott-Aldrich syndrome?

A genetic change (mutation) of the WAS gene causes Wiskott-Aldrich syndrome. WAS is located on the short arm of your X chromosome. This gene is responsible for producing the Wiskott-Aldrich syndrome protein. This protein exists in all of your blood cells.

The Wiskott-Aldrich syndrome protein tells your cells to attach to other cells and tissues in a process called adhesion. Adhesion helps your immune system defeat invaders like bacteria or viruses, which can make you sick.

If you have a genetic mutation on the WAS gene, your blood cells aren't able to attach to other cells and tissues. This can affect how your immune system defends itself, which results in the symptoms of Wiskott-Aldrich syndrome.

In congenital neutropenia, the genetic mutation causes neutrophils and monocytes to stall in their movement. Your immune system then doesn't release them to fight infection.

Can you inherit Wiskott-Aldrich syndrome?

Yes, you can inherit Wiskott-Aldrich syndrome. This condition has an X-linked recessive pattern of inheritance where you get the genetic change from both of your biological parents.

You inherit one sex chromosome from each of your biological parents. People AMAB have one X and one Y sex chromosome and people AFAB have two X chromosomes. The condition affects people because the mutation affects the function of their only X chromosome.

The condition does have a pattern of inheritance in biological families, but over 30% of all cases occur without a presence in your biological family history (de novo). These cases are the result of a new genetic mutation that happens during conception.

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Wiskott-Aldrich syndrome is a rare genetic condition that affects your child's immune system, blood cells and skin.

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Immunodeficiency disorders are either congenital or acquired. A congenital, or primary, disorder is one you were born with. An acquired, or secondary, disorder is one you get later in life. Acquired disorders are more common than congenital disorders.

What causes immunodeficiency?

Primary immunodeficiency disorders are most commonly caused by inherited gene mutations. Secondary immunodeficiency disorders can be caused by a variety of things, including chronic conditions (like diabetes or cancer), drugs, radiation therapy (which is rare), long-term hospitalization, insufficient nutrition.

References:

Immunodeficiency Disorders: Symptoms, Types, and More (healthline.com)

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Immunodeficiency disorders prevent your body from fighting infections and diseases. This type of disorder makes it easier for you to catch viruses and bacterial infections.

Immunodeficiency disorders are either congenital or acquired. A congenital, or primary, disorder is one you were born with. An acquired, or secondary, disorder is one you get later in life. Acquired disorders are more common than congenital disorders.

Your immune system includes the following organs:

These organs process and release lymphocytes. These are white blood cells classified as B cells and T cells. B and T cells fight invaders called antigens. B cells release antibodies specific to the disease your body detects. Certain T cells destroy foreign or atypical cells.

Examples of antigens that your B and T cells might need to fight off include:

An immunodeficiency disorder disrupts your body's ability to defend itself against these antigens.

What is a weak immune system?

If you have a weaker immune system, you're immunocompromised. This means your body can't fight off infections or viruses as well as people who are not immunocompromised.

While a weaker immune system is typically caused by certain diseases, malnutrition, and certain genetic disorders, it can also temporarily be caused by medications such as anticancer drugs and radiation therapy.

Your immune system can also be temporarily weakened by a stem cell or organ transplant.

There are hundreds of forms of immunodeficiency disorders. Each disorder has unique symptoms that can be frequent or chronic. However, there are a few warning signs that something may be going on with your immune system.

Individuals with immunodeficiency disorders tend to have frequent infections - one round after another - of certain conditions, such as:

Individuals with immunodeficiency disorders may also develop chronic abdominal pain, and they may even lose weight over time.

If you find that you get sick easily and have a hard time shaking off viruses and other infections, your doctor might test you for an immunodeficiency disorder.

An immune deficiency disease or disorder occurs when the immune system is not working as expected. If you're born with a deficiency from a genetic cause, it's called primary immunodeficiency disease. There are more than 200 primary immunodeficiency disorders.

Examples of primary immunodeficiency disorders include:

common variable immunodeficiency (CVID)

severe combined immunodeficiency (SCID), which is also known as alymphocytosis

chronic granulomatous disease (CGD)

Secondary immunodeficiency disorders happen when an outside source like a chemical or infection weakens your body. The following can cause a secondary immunodeficiency disorder:

Examples of secondary immunodeficiency disorders include:

Primary immunodeficiency disorders are most commonly caused by inherited gene mutations.

Secondary immunodeficiency disorders can be caused by a variety of things, including:

chronic conditions (like diabetes or cancer)

drugs

radiation therapy (this is rare)

long-term hospitalization

insufficient nutrition

Risk factors

People who have a family history of primary immunodeficiency disorders have a higher risk for developing primary disorders themselves.

Anything that weakens your immune system can lead to a secondary immunodeficiency disorder. For example, exposure to body fluids infected with HIV or organ removal and replacement can both be causes.

Aging can also weaken your immune system. As you age, some of the organs that produce or process white blood cells shrink and become less efficient.

Proteins are important for your immunity. Not enough protein in your diet can weaken your immune system.

Your body also produces proteins when you sleep that help your body fight infection. For this reason, lack of sleep can reduce your immune defenses.

Cancers and chemotherapy drugs can also reduce your immunity.

If your doctor thinks you might have an immunodeficiency disorder, they will want to:

Your doctor may also perform a skin test, which is usually performed when a T-cell abnormality is suspected.

During a skin test, a small number of proteins from common infectious organisms (like yeast) are injected right under the skin. If there's not a reaction (swelling or redness) within 2 days, that can be a sign of an immunodeficiency disorder from a T-cell abnormality.

Biopsies of the lymph nodes or bone marrow may also be performed to help your doctor narrow down which disorder may be causing your symptoms.

Genetic testing, usually via a blood test, to determine if there are any gene mutations that are causing your immunodeficiency disorder may also be ordered.

Treating immunodeficiency disorders typically revolves around:

preventing infections when possible

treating infections when they occur

strengthening parts of the immune system

Antibiotics and immunoglobulin therapy are two types of medications often used in treatment.

Other antiviral drugs, like oseltamivir and acyclovir, or a drug called interferon are sometimes used for treatment of the viral infections caused by immunodeficiency disorders.

If your bone marrow isn't producing enough lymphocytes, your doctor might order a bone marrow (stem cell) transplant.

Primary immunodeficiency disorders can be managed and treated, but they can't be prevented.

The risk of developing secondary disorders can sometimes be lowered through lifestyle choices. For example, it's possible to lower your risk of developing type 2 diabetes by eating a nutritious diet and getting adequate physical activity.

Sleep is very important for a healthy immune system. According to the CDC, prolonged sleep loss may not only lead to a variety of chronic conditions, it may also weaken your body's ability to fight off infections.

If your primary care physician has diagnosed you with an immunodeficiency disorder, or suspects you might have one and wants an expert opinion, they will most likely send you to an immunologist.

Immunologists specialize in immunodeficiency disorders. Typically, after acquiring a bachelor's degree, individuals who want to become immunologists must go through 9 years of additional medical training.

To be board certified, they must pass an exam given by the American Board of Allergy and Immunology (ABAI).

If you've been diagnosed with an immunodeficiency disorder, it means that your immune system is not able to fight off infections or viruses effectively. You may have been born with it, or it could have arisen later in life due to a chronic condition, such as diabetes or cancer.

There are hundreds of forms of immunodeficiency disorders. According to the British Society for Immunology, approximately 6 million people worldwide live with a primary immunodeficiency disorder (i.e., they were born with it).

Most doctors agree that people with immunodeficiency disorders can lead full and productive lives. Early identification and treatment of the disorder is very important.

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Immunodeficiency Disorders: Symptoms, Types, and More

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Everything you need to know about immunodeficiency disorders, including types, causes, and symptoms.

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Available treatments for Wiskott-Aldrich Syndrome (Darius)

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Available treatments for Wiskott-Aldrich Syndrome (Darius)

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For Wiskott-Aldrich syndrome (WAS), treatment focuses on managing symptoms and preventing complications.

Firstly, there is bone marrow transplantation which involves replacing the patient’s faulty bone marrow with healthy bone marrow from a compatible donor and includes pre-transplant conditioning (chemotherapy or radiation) to prepare the patient’s body and to make space for the new stem cells. Successful transplantation can restore normal blood cell production and immune function. However, it carries risks such as graft-versus-host disease (GVHD), infections, and other complications.

Secondly, there is Immunoglobulin therapy, it involves intravenous immunoglobulin (IVIG) infusions provide antibodies that help fight infections. This therapy is typically used to support patients with immune deficiency to boost the immune system and help prevent infections.

Lastly, there is platelet transfusions which involves platelet transfusions that help temporarily increase platelet levels and reduce bleeding risk, but they do not address the underlying cause of the low platelet count.

References:

Wiskott-Aldrich Syndrome (nih.gov)

Wiskott-Aldrich Syndrome - StatPearls - NCBI Bookshelf (nih.gov)

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Which branch of immunity is affected for Wiskott-Aldrich Syndrome (Teck Zheng)

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Which branch of immunity is affected for Wiskott-Aldrich Syndrome (Teck Zheng)

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Effects on Innate Immunity

The innate immune system, our body's first line of defense against pathogens, is substantially affected in WAS patients.

Natural Killer (NK) Cells

Natural killer cells in WAS patients exhibit impaired function due to defective immunological synapse formation. The immunological synapse is a specialized cell-cell junction between an immune cell and a target cell, crucial for NK cell-mediated cytotoxicity. In WAS, the inability to properly form this synapse significantly hampers the NK cells' ability to recognize and eliminate infected or malignant cells.

Invariant Natural Killer T (iNKT) Cells

Perhaps one of the most striking effects of WAS on innate immunity is the complete absence of invariant natural killer T cells in affected individuals. These cells play a vital role in bridging innate and adaptive immunity and are important in regulating immune responses. Their absence contributes to the complex immunodeficiency observed in WAS patients.

Neutrophils

Neutrophils, the most abundant type of white blood cells, also show functional deficits in WAS. These cells display abnormal migration and motility, which can impair their ability to reach sites of infection and effectively combat pathogens. This defect is attributed to the role of WASp in regulating actin polymerization, which is crucial for cell movement.

Effects on Adaptive Immunity

The adaptive immune system, responsible for targeted and memory responses to specific pathogens, is also significantly impacted in WAS.

T Cells

T cell function is markedly compromised in WAS patients. The abnormal cytoskeleton reorganization in these cells leads to impaired adhesion and interaction with other immune cells. This affects various T cell functions, including activation, proliferation, and cytokine production. Moreover, the formation of the immunological synapse between T cells and antigen-presenting cells is disrupted, further compromising T cell-mediated immunity.

B Cells

B cell homeostasis is severely affected in WAS. There is a selective depletion of circulating mature B cells and splenic marginal zone B cells. This depletion is thought to result from increased apoptosis and decreased survival of these cells. The marginal zone B cells are particularly important for rapid antibody responses to blood-borne pathogens, and their loss contributes to the increased susceptibility to infections seen in WAS patients.

Antibody Production

Antibody responses in WAS patients are abnormal, with IgM deficiency being particularly common. This deficiency affects the ability to mount effective responses against encapsulated bacteria. Additionally, patients often show poor responses to polysaccharide antigens and may have difficulty maintaining long-term antibody responses, indicating problems with immunological memory.

References:

https://www.ncbi.nlm.nih.gov/books/NBK539838/

https://emedicine.medscape.com/article/137015-overview?form=fpf

https://radiopaedia.org/articles/wiskott-aldrich-syndrome-2

https://www.msdmanuals.com/en-sg/professional/immunology-allergic-disorders/immunodeficiency-disorders/wiskott-aldrich-syndrome

https://medlineplus.gov/genetics/condition/wiskott-aldrich-syndrome/

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Frequency
United States
The incidence of classic WAS phenotype has been estimated at 1 and 10 in 1 million cases per live birth. Overall, WAS accounts for about 3% of all primary immunodeficiency disorders.
International
A study from Switzerland reported the incidence of WAS is 4.1 cases per 1 million live births. The same study also examined the prevalence of WAS in several national registries (ie, Italy, Japan, Switzerland, Sweden) and found that this condition occurred in 2-8.8% of patients with primary immunodeficiencies, although this statistic is subject to ascertainment bias.A similar range has been documented in a national registry in Ireland, as well.

Mortality/Morbidity

Median survival has increased from 8 months (patients born before 1935) to longer than 6 years (patients born after 1964).In one case series, 94 surviving patients ranged in age from 1-35 years, with a median of 11 years; the average age of patients who died was 8 years.

The cause of death is largely infections or bleeding, but, in one series, 12% of patients developed malignancies, primarily B-cell lymphomas, and leukemia. In that series, the relative risk of malignancy was more than 100-fold that of normal and the risk increased with age.Another study showed similar results, with the reported cause of death among patients who did not receive bone marrow transplants being infection (44%), bleeding (23%), or malignancy (26%).

With aggressive care (eg, splenectomy), longer survival is possible.Bone marrow transplant can be curative.Survival rates after stem cell transplant have continued to increase, particularly after more recent emphasis on performing these procedures as soon as possible after diagnosis.

Outcomes of hematopoietic cell transplantation have especially improved since 2000. From the most recent series of transplanted patients, overall survival from HSCT was approximately 90%.

Race-, sex-, and age-related characteristics

One large series of 301 confirmed and probable cases of WAS from 149 families reported that 8 families were black and 4 families were Chicano. Of the 40 families whose ancestry was traced outside North America, 38 emigrated from Europe.

WAS is an X-linked recessive genetic disorder. The abnormal gene is relatively rare, and untreated individuals often do not survive childhood.

WAS occurs almost exclusively in males, although it is also reported in females. One report of WAS in an 8-year-old girl found a WASp gene mutation on her paternal X chromosome associated with nonrandom inactivation of her maternal X chromosome.Other closely related genetic abnormalities (such as WIP deficiency) have also been reported in females, with clinical features similar to WAS.

WAS is a severe congenital immunodeficiency; therefore, it occurs primarily in children. However, 2 large case series reported patients in their fourth decade of life.

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Wiskott-Aldrich syndrome (WAS) is a condition with variable expression, but commonly includes immunoglobulin M (IgM) deficiency. WAS always causes persistent thrombocytopenia and, in its complete form, also causes small platelets, atopy, cellular and humoral immunodeficiency, and an increased risk of autoimmune disease and hematologic maligna...

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Reflections of how the functions of immune components are important in reference to Wiskott-Aldrich Syndrome (WAS) (jiaxin)

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Reflections of how the functions of immune components are important in reference to Wiskott-Aldrich Syndrome (WAS) (jiaxin)

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Immune components involved in Wiskott-Aldrich Syndrome (WAS) include:

Wiskott-Aldrich Syndrome Protein (WASP):

WAS is caused by mutations occurring in the WASP gene, which is the gene responsible for coding the WASP protein. WASP is crucial for the regulation of actin cytoskeleton-dependent cellular processes as well as processes uncoupled with actin polymerization like nuclear transcription programs.

WASP is important for the function and activation of immune cells like T cells and B cells in the immune system as intact cytoskeleton network is required for many of the cellular processes that they go through, like migration, adhesion and signal transduction.

Hence the absence or dysfunction of WASP impairs cell signaling and movement, affecting the overall immune response.

T-cell:

Defective T-cell responses caused by the mutations of WASP affects the recognition and response to pathogens, regulation of immune responses, and the assistance in the activation of other immune cells. to opportunistic pathogens and certain viruses and bacteria.

Dysfunction of T-cells leads to an increased vulnerability to infections, especially

B-cell:

Defective B-cell responses caused by the mutations of WASP affects normal antibody production and responses to antigens.

Dysfunction of B-cells leads to an increased vulnerability to infections. The body is also not able to mount effective antibody defenses.

Platelet:

Thrombocytopenia is a symptom of WAS, and it is a condition in which a patient has low platelet counts.

Platelets play a crucial role in immune response. They are involved in hemostasis, helping with blood clotting and wound healing. They also interact with immune cells, influencing their cell activation and function.

Thrombocytopenia leads to bleeding disorders and increased susceptibility to infections due to a compromised immune system.

The combined dysfunction of immune components involved in the Wiskott-Aldrich Syndrome can lead to inefficient pathogen clearance, leading to recurrent and more severe infections.

References:

https://www.sciencedirect.com/topics/neuroscience/wiskott-aldrich-syndrome-protein

https://pubmed.ncbi.nlm.nih.gov/31047647/#:~:text=WASp%20functions%20in%20immune%20defense,polymerization%20like%20nuclear%20transcription%20programs.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327460/

https://www.mayoclinic.org/diseases-conditions/thrombocytopenia/symptoms-causes/syc-20378293#:~:text=Thrombocytopenia%20is%20a%20condition%20in,plugs%20in%20blood%20vessel%20injuries.

https://www.childrenshospital.org/conditions/wiskott-aldrich-syndrome#:~:text=Because%20the%20B%20cells%20of,with%20a%20weakened%20immune%20system.

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Wiskott-Aldrich Syndrome | 2-Minute Immunology | USMLE | V-Learning™