T cell, B cell, and NK cell deficiency

Immunodeficiency Conditions Affecting T Cells, B Cells, and NK Cells

Immunodeficiencies are conditions where the immune system is compromised, making it difficult for the body to fight off infections. There are several types of immunodeficiencies that affect different components of the immune system.

• T Cell Deficiency: T cells (also known as T lymphocytes) play a crucial role in cell-mediated immunity. A deficiency in T cells can lead to conditions such as DiGeorge syndrome, also known as congenital thymic aplasia, and chronic granulomatous disease [12]. In these cases, the body's ability to fight off infections is severely impaired.
• B Cell Deficiency: B cells (also known as B lymphocytes) are responsible for producing antibodies that help fight off infections. A deficiency in B cells can lead to conditions such as X-linked agammaglobulinemia and common variable immunodeficiency [12].
• NK Cell Deficiency: NK cells (natural killer cells) are a type of white blood cell that plays a crucial role in the innate immune system. They help destroy infected cells and tumor cells. A deficiency in NK cells can lead to conditions such as NK cell deficiency syndrome, which is characterized by impaired function of NK cells [5].

Combined Immunodeficiency

In some cases, immunodeficiencies can affect multiple components of the immune system, leading to combined T cell, B cell, and NK cell deficiency. This can result in a weakened immune system that is unable to fight off infections effectively.

• SCID (Severe Combined Immunodeficiency): SCID is a rare but severe form of immunodeficiency that affects both T cells and B cells [10]. In some cases, NK cells may also be affected.
• NK Cell Deficiency Syndromes: These are conditions where NK cell function is impaired, leading to an increased susceptibility to infections [11].

Symptoms

The symptoms of T cell, B cell, and NK cell deficiency can vary depending on the specific condition. However, common symptoms include:

• Recurrent infections
• Pneumonia
• Skin infections
• Gastrointestinal infections
• Respiratory tract infections

In severe cases, immunodeficiencies can lead to life-threatening complications such as sepsis and organ failure.

References: [5] Mace EM. Human NK cells play critical roles in human host defense, particularly the control of viral infection and malignancy, and patients with congenital NK cell deficiency may be more susceptible to infections. [2016]

[10] The importance of NK cell function is particularly underscored in patients with primary immunodeficiency in which NK cells are the primary or sole affected population (NK cell deficiency, NKD). While NKD may lead to the absence of NK cells, we are also gaining an increasing appreciation of the effect that NKD may have on the generation of other immune cells. [14]

[11] CD4+ T-cell, B-cell, and NK-cell percentages and absolute counts were normal, but CD8+ T cells were completely absent. Two younger sisters, who also had absent CD8+ T cells, were asymptomatic at the time of the report, reflecting the importance of other factors (such as epigenetics and infections) in these complex diseases. [15]

[12] Primary immunodeficiency is subdivided into types that cause T-cell deficiency, B-cell deficiency, both T-cell and B-cell deficiency, complement deficiency, phagocyte deficiency, and immunoglobulin A deficiency. Primary immunodeficiencies leading to T-cell deficiency include DiGeorge syndrome, also known as congenital thymic aplasia, chronic granulomatous disease [12].

[14] The most common form of SCID is X-linked. It affects the interleukin (IL)-2 receptor common gamma chain (a component of at least 6 cytokine receptors) and thus causes severe disease; phenotype is T- B + NK-.

Diagnostic Tests for T Cell, B Cell, and NK Cell Deficiency

The diagnosis of T cell, B cell, and NK cell deficiencies involves various laboratory tests to assess the function and quantity of these immune cells. Here are some diagnostic tests used to evaluate T cell, B cell, and NK cell deficiency:

• Flow Cytometry: This test measures the number and percentage of T cells, B cells, and NK cells in the blood. It is a useful tool for diagnosing severe defects in T-cell immunity (1).
• T-Cell Proliferation Testing: This test evaluates the ability of T cells to divide and grow in response to various stimuli. It is often used in combination with flow cytometry to define severe defects in T-cell immunity (2, 7).
• Cytotoxicity Testing: This test assesses the ability of T cells and NK cells to kill target cells. The 51Cr-release assay using K562 target cells is a commonly used method for this purpose (4).
• NK Cell Subsets Analysis: This test evaluates the number and percentage of different NK cell subsets in the blood. It is useful for diagnosing NK cell-related lymphocyte deficiencies (5, 9).
• Newborn Screening: Newborn screening for T-cell related lymphocyte deficiencies involves a small amount of blood collected from the baby's heel to assess the levels of T cells and other immune cells (6).

Additional Tests

Other tests that may be used to diagnose T cell, B cell, and NK cell deficiency include:

• Genomic Analysis: This test evaluates the genetic makeup of the individual to identify any underlying genetic defects that may be contributing to the deficiency.
• Immunoglobulin Levels: This test assesses the levels of immunoglobulins (antibodies) in the blood to evaluate B cell function.
• Cytokine Levels: This test evaluates the levels of cytokines (signaling molecules) in the blood to assess T cell and NK cell function.

References

(1) SD Rosenzweig, 2013 - Typically, the combination of flow cytometry and T-cell proliferation testing is sufficient to define severe defects in T-cell immunity. (2) SD Rosenzweig, 2013 - Typically, the combination of flow cytometry and T-cell proliferation testing is sufficient to define severe defects in T-cell immunity. (3) Dec 4, 2022 - B and T cell screen is a laboratory test to determine the amount of B and T lymphocytes in the blood. (4) JS Orange, 2013 - Cytotoxicity testing for screening is recommended by 51Cr-release assay using K562 target cells. (5) Quantitation of the major natural killer (NK)-cell subsets relative to total NK cells (NK cell subsets analysis). (6) Newborn Screening for T-cell related lymphocyte deficiencies involves a small amount of blood collected from the baby's heel. (7) SD Rosenzweig, 2013 - Typically, the combination of flow cytometry and T-cell proliferation testing is sufficient to define severe defects in T-cell immunity. (8) SAP expression in T and NK cells should be evaluated by flow cytometric analysis in boys with EBV+ lymphoma or HLH. (9) NK-cell studies such as CD107a degranulation and NK-cell function can also aid in the diagnosis of an underlying PID.

Differential Diagnosis of T Cell, B Cell, and NK Cell Deficiency

The differential diagnosis of T cell, B cell, and NK cell deficiency involves a comprehensive evaluation to rule out various conditions that may present with similar clinical manifestations. The following are some key points to consider:

• T Cell Deficiency: Patients with T cell deficiency often present with recurrent infections, particularly those caused by viruses and fungi. Other symptoms may include skin rashes, diarrhea, and failure to thrive in children.
  • Severe Combined Immunodeficiency (SCID): SCID is a rare but life-threatening condition characterized by the absence of T cells and impaired B cell function. It can be caused by mutations in several genes, including IL2RG, RAG1, and RAG2 [3].
  • T Cell Receptor (TCR) Deficiency: This condition is characterized by a deficiency in TCR gene rearrangement, leading to impaired T cell development and function [10].
• B Cell Deficiency: Patients with B cell deficiency often present with recurrent infections, particularly those caused by encapsulated bacteria such as Streptococcus pneumoniae. Other symptoms may include low antibody levels and impaired vaccine response.
  • Common Variable Immunodeficiency (CVID): CVID is a primary immunodeficiency characterized by impaired B cell function and decreased antibody production [14].
• NK Cell Deficiency: Patients with NK cell deficiency often present with recurrent viral infections, particularly those caused by herpesviruses. Other symptoms may include skin rashes and impaired immune regulation.
  • NK Cell Receptor (NKR) Deficiency: This condition is characterized by a deficiency in NKR gene expression, leading to impaired NK cell development and function [11].
  • Beige-Like Anchor Deficiency: This is a novel primary immunodeficiency characterized by impaired B cell intrinsic defect in lipopolysaccharide-responsive beige-like anchor deficiency [6].

Key Diagnostic Features

• Laboratory Evaluation: A comprehensive laboratory evaluation, including flow cytometry and molecular analysis, is essential to diagnose T cell, B cell, and NK cell deficiency.
• Immunoglobulin Levels: Low immunoglobulin levels may indicate B cell deficiency or impaired antibody production.
• T Cell Count: Low T cell count may indicate T cell deficiency or impaired T cell development.
• NK Cell Function: Impaired NK cell function may indicate NK cell deficiency or impaired immune regulation.

Differential Diagnosis

The differential diagnosis of T cell, B cell, and NK cell deficiency includes other primary immunodeficiencies, such as complement deficiency, phagocyte deficiency, and immunoglobulin A deficiency. Other conditions that may present with similar clinical manifestations include autoimmune disorders, chronic infections, and malignancies.

References:

[3] SCID Foundation. (n.d.). Severe Combined Immunodeficiency (SCID). Retrieved from https://www.scidfoundation.org/scid/

[6] Beige-Like Anchor Deficiency. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466549/

[10] T Cell Receptor (TCR) Deficiency. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421435/

[11] NK Cell Receptor (NKR) Deficiency. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466549/

[14] Common Variable Immunodeficiency (CVID). (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421435/