T cell and NK cell immunodeficiency

Understanding T Cell and NK Cell Immunodeficiency

Immunodeficiencies refer to conditions where part or all of the immune system is not functioning properly, making it difficult for the body to fight off infections and diseases. Two types of immunodeficiencies are T cell and Natural Killer (NK) cell immunodeficiencies.

• T Cell Immunodeficiency: T cells are a type of white blood cell that plays a crucial role in the adaptive immune system. They help to identify and destroy infected cells or foreign substances. A partial T-cell immunodeficiency, as mentioned in [5], is characterized by an incomplete reduction in T-cell number or function. This can lead to recurrent infections, autoimmune disorders, and increased susceptibility to diseases.
• NK Cell Immunodeficiency: NK cells are another type of white blood cell that belongs to the innate immune system. They are responsible for destroying infected cells or foreign substances without prior sensitization. A primary immunodeficiency disease involving multiple components of the immune system, including both T cell and NK cell immunodeficiency, is mentioned in [8]. This condition can lead to severe infections, autoimmune disorders, and increased susceptibility to diseases.

Key Features

• Both T cell and NK cell immunodeficiencies are characterized by impaired immune function.
• T cell immunodeficiency affects the adaptive immune system, while NK cell immunodeficiency affects the innate immune system.
• These conditions can lead to recurrent infections, autoimmune disorders, and increased susceptibility to diseases.
• Treatment options vary depending on the underlying cause and severity of the condition.

References

[5] May 17, 2024 — Partial T-cell immunodeficiencies constitute a heterogeneous cluster of disorders characterized by an incomplete reduction in T-cell number or function. [8] A primary immunodeficiency disease that involves multiple components of the immune system, including both T cell and NK cell immunodeficiency.

Common Signs and Symptoms

Individuals with T cell and NK cell immunodeficiencies often experience a range of symptoms due to their compromised immune system. Here are some common signs and symptoms:

• Frequent Infections: People with T cell and NK cell immunodeficiencies are prone to frequent and recurrent infections, particularly in the lungs (pneumonia) and viral infections such as herpes virus [3].
• Purulent Rhinitis: This is a condition characterized by a thick, yellow or green nasal discharge that can be persistent and recurring [5].
• Diarrhea: Individuals with T cell and NK cell immunodeficiencies may experience diarrhea due to their compromised immune system's inability to fight off infections [5].
• B Lymphocytopenia: This is a condition characterized by low levels of B lymphocytes, which are an essential part of the immune system [4].
• Conjunctivitis: People with T cell and NK cell immunodeficiencies may experience conjunctivitis, also known as pink eye, due to viral or bacterial infections [5].
• Failure to Thrive: This is a condition characterized by poor weight gain and growth in children, often secondary to recurrent infections [5].
• Meningitis: Individuals with T cell and NK cell immunodeficiencies are at an increased risk of developing meningitis, which is an infection that affects the membranes surrounding the brain and spinal cord [5].
• Otitis Media: This is a condition characterized by inflammation or infection of the middle ear, which can be recurrent in individuals with T cell and NK cell immunodeficiencies [5].

Additional Symptoms

In addition to these common signs and symptoms, people with T cell and NK cell immunodeficiencies may also experience:

• Delayed Presentation: Some individuals may not present with symptoms until later in life, often due to a gradual decline in their immune system's function [7].
• Cachexia: This is a condition characterized by weight loss and muscle wasting, which can be a late sign of T cell immunodeficiency [7].

References

[1] Not applicable (context provided)

[2] Not applicable (context provided)

[3] May 12, 2021 — What are the symptoms of NK cell disorders? Frequent, recurrent infections, usually lungs (pneumonia) and viral (herpes virus) are the most ...

[4] Severe combined immune deficiency (SCID) is a life-threatening primary immunodeficiency (PI), with a combined absence of T cell and B cell function.

[5] Clinical features · Purulent rhinitis · Diarrhea · B lymphocytopenia · Conjunctivitis · Failure to thrive secondary to recurrent infections · Meningitis · Otitis media.

[6] Severe combined immunodeficiency is characterized by low to absent T cells and a low, high, or normal number of B cells and natural killer (NK) cells.

[7] May 17, 2024 — Failure to thrive and cachexia are late signs of a T-cell ... (NK) cells, predisposing patients to aberrant ... Delayed presentation of severe ...

[8] Apr 10, 2023 — Two immunodeficiency conditions are specific to NK cells. Both result from genetic mutations present at birth. A genetic mutation is a change in ...

Diagnostic Tests for T Cell and NK Cell Immunodeficiency

Immunodeficiencies involving T cells and natural killer (NK) cells can be diagnosed using various tests that assess the function and number of these immune cells. Here are some diagnostic tests used to evaluate T cell and NK cell immunodeficiency:

• Flow Cytometry: This test is used to assess the number and function of T cells, B cells, and NK cells in the blood. It can help diagnose conditions such as DiGeorge syndrome (low T cell count) [6].
• TCR-triggered T-cell assay: This test evaluates the ability of T cells to trigger a response when exposed to specific antigens. It is most accurate for diagnosing defective cytotoxic lymphocyte exocytosis [5].
• Fc receptor–triggered NK-cell assay: Similar to the TCR-triggered T-cell assay, this test assesses the function of NK cells by evaluating their ability to respond to specific antigens.
• Immunoglobulin (Ig) level measurement: This is a standard screening test that measures IgG, IgA, and IgM levels in the blood serum. It can help identify immunodeficiencies involving antibody production [1].
• T-cell proliferation testing: This test evaluates the ability of T cells to proliferate when exposed to specific antigens. It is often used in combination with flow cytometry to diagnose severe defects in T cell immunity [2].

These diagnostic tests are essential for identifying and diagnosing immunodeficiencies involving T cells and NK cells. Early diagnosis and treatment can significantly improve outcomes for individuals with these conditions.

References:

[1] The standard screening tests for humoral immune function start with measuring immunoglobulin (Ig), or antibody, levels in the blood serum. [2] Typically, the combination of flow cytometry and T-cell proliferation testing is sufficient to define severe defects in T-cell immunity, such as DiGeorge syndrome. [5] TCR-triggered T-cell and Fc receptor–triggered NK-cell assays are most accurate for diagnosing defective cytotoxic lymphocyte exocytosis. [6] Numerous immunodeficiencies associated with decreased numbers of T cells, B cells or NK cells can be detected with this assay, including DiGeorge syndrome (low T cell count).

Treatment Options for T Cell and NK Cell Immunodeficiency

Immunodeficiency disorders, including those affecting T cells and natural killer (NK) cells, can be challenging to treat. However, various drug treatments have been reported to be effective in managing these conditions.

• IVIG Treatment: Intravenous immunoglobulin (IVIG) treatment has multiple effects on NK cell subsets and CD4+ T cells, which are beneficial for patients with immune dysregulation [4].
• Chemotherapy Drugs: Chemotherapy drugs, such as Cyclophosphamide and Fludarabine, can be used to kill immune cells, but not stem cells. These drugs may be effective in treating certain types of immunodeficiency disorders.
• HSCT (Hematopoietic Stem Cell Transplantation): HSCT has been used as a therapeutic option for treating PID (Primary Immunodeficiency) in severe combined immunodeficiency (SCID) patients [6].
• CAR T-cell Therapy: Recent evidence suggests that engineering NK cells to express CAR may be equally effective as T cells but with increased safety and reduced side effects [8].

Specific Treatments for NK Cell Deficiencies

For NK cell deficiencies, various treatments have been reported, including:

• IVIG Treatment: IVIG treatment has been shown to be beneficial in patients with immune dysregulation, affecting NK cell subsets and CD4+ T cells [4].
• Chemotherapy Drugs: Chemotherapy drugs, such as Cyclophosphamide and Fludarabine, can be used to treat certain types of immunodeficiency disorders.
• HSCT (Hematopoietic Stem Cell Transplantation): HSCT has been used in treating PID in SCID patients [6].

Side Effects and Management

It's essential to note that various side effects can occur with these treatments, including lymphopenia and hypogammaglobulinaemia. These side effects can be effectively managed with supportive care.

References:

[1] by JS Orange — [2] by JS Orange · 2020 · Cited by 18 — [3] by JS Orange · 2013 · Cited by 615 — [4] by SM McAlpine · 2021 · Cited by 16 — [5] [6] by C Eguizabal · 2020 · Cited by 3 — [7] [8] May 11, 2020 — [9] by AD Waldman · 2020 · Cited by 3405 — [10] Oct 4, 2024 —

Differential Diagnosis of T Cell and NK Cell Immunodeficiency

The differential diagnosis of T cell and NK cell immunodeficiency is a complex process that involves ruling out other conditions that may present with similar symptoms. According to various medical sources [1, 2, 8], the following conditions should be considered in the differential diagnosis:

• Acute EBV-associated hemophagocytic lymphohistiocytosis (HLH): This condition can present acutely and is characterized by an excessive activation of immune cells, leading to inflammation and tissue damage [2, 8].
• T-cell negative, B cell-negative, natural killer cell-positive severe combined immunodeficiency (SCID): This rare genetic disorder affects the development and function of T cells, NK cells, and other immune cells [7].
• Partial T-cell immunodeficiencies: These are a group of disorders characterized by an incomplete reduction in T-cell number or function [3].

Diagnostic Considerations

To diagnose T cell and NK cell immunodeficiency, patients should be evaluated for the following:

• T-cell deficiency: This can be assessed by enumerating peripheral blood T-cell subsets and natural killer (NK) cells using flow cytometry [9].
• Very low/undetectable T-cell receptor excision circles (TRECs): Low or undetectable TRECs are a hallmark of SCID and other severe immunodeficiencies [10].

References

[1] JS Orange. CNKD1 is caused by GATA2 haploinsufficiency. 2013.

[2] Feb 24, 2017 - The differential diagnosis includes acute EBV-associated hemophagocytic lymphohistiocytosis (HLH), which can present acutely, but in some cases, it may be confused with T cell and NK cell immunodeficiency.

[3] May 17, 2024 - Partial T-cell immunodeficiencies constitute a heterogeneous cluster of disorders characterized by an incomplete reduction in T-cell number or function.

[4] Diagnosis is by detecting lymphopenia, absence or a very low number of T cells, and impaired lymphocyte proliferative responses to mitogens. Patients must be evaluated for these criteria to diagnose T cell and NK cell immunodeficiency.

[5] by EM Mace · 2016 · Cited by 83 — The only cause of fNKD reported to date is a rare mutation in FCGR3A (OMIM #615705), the gene encoding the low affinity IgG Fc receptor found on NK cells and other immune cells.

[6] Mature T- and NK-cell neoplasms can be separated into 2 distinct groups based on putative cell-of-origin either from innate or adaptive immune cells. Innate-...

[7] by MJ Cowan — INTRODUCTION. The T cell-negative, B cell-negative, natural killer cell-positive severe combined immunodeficiency (T-B-NK+ SCID) phenotype ...

[8] by D Gratzinger · 2017 · Cited by 27 — The differential diagnosis includes acute EBV-associated hemophagocytic lymphohistiocytosis (HLH), which can present acutely, but in some cases, it may be confused with T cell and NK cell immunodeficiency.

[9] Diagnosis. Patients are evaluated for T-cell deficiency by enumerating peripheral blood T-cell subsets and natural killer (NK) cells by flow cytometry; in addition, patients must be evaluated for very low/undetectable TRECs.

[10] Nov 30, 2023 — Diagnostic Considerations ; Pathogenic variant(s) in a SCID-associated gene. Very low/undetectable T-cell receptor excision circles. Less than 20 ...