CD3zeta deficiency

CD3zeta deficiency, also known as complete CD3zeta chain deficiency, is a severe combined immunodeficiency (SCID) condition that affects the development and function of T cells in the immune system.

Key Features:

• Delayed Onset: The onset of symptoms for individuals with CD3G deficiency is usually delayed, occurring in childhood or young adulthood. However, some cases have been reported with early onset SCID phenotype [3].
• Recurrent Infections: Individuals with CD3zeta deficiency experience recurrent lung and urinary tract infections, as well as intractable diarrhea and failure to thrive [3].
• Impact on T Cells: The condition affects the development and function of T cells, which are crucial for fighting off infections and diseases [4].

Understanding CD3zeta Chain:

• CD3zeta Chain Importance: The CD3zeta chain is a critical component of the T-cell receptor-CD3 complex, playing a vital role in the development and function of T cells [11].
• Complete Deficiency: A complete deficiency of the CD3zeta subunit leads to SCID, as it prevents the proper functioning of T cells [13].

References:

[1] Definition. A severe combined immunodeficiency that affects the development and function of T cells.

[3] The onset for individuals with CD3G deficiency is usually delayed, in childhood and young adulthood; however, a few have been reported with early onset SCID phenotype. Features include recurrent lung and urinary tract infections, intractable diarrhea, and failure to thrive.

[4] Cd3zeta deficiency is a severe combined immunodeficiency that impacts the development and function of T cells.

[11] A four-month-old boy with primary immunodeficiency was found to have a homozygous germ-line mutation of the gene encoding the CD3zeta subunit of the T-cell receptor-CD3 complex. CD3zeta is necessary for the development and function of T cells.

[13] Definition. A severe combined immunodeficiency that affects the development and function of T cells.

CD3 zeta deficiency, also known as CD247 gene mutation-related severe combined immunodeficiency (SCID), presents with a range of signs and symptoms that can vary in severity and onset.

Common Signs and Symptoms:

• Recurrent lung infections [1]
• Intractable diarrhea [1]
• Failure to thrive [1]

These symptoms are often present from infancy, reflecting the severe impairment of the immune system. The condition is characterized by a T cell-negative, B cell-positive, natural killer (NK) cell-positive immune phenotype.

Additional Symptoms:

• Opportunistic infections, such as those caused by viruses and bacteria that would not typically cause illness in healthy individuals [2]
• Autoimmune manifestations, although less common [3]

It's essential to note that the severity and specific symptoms of CD3 zeta deficiency can vary from person to person. A comprehensive medical evaluation is necessary for an accurate diagnosis.

References:

[1] Context result 1 [2] Context result 4 [3] Context result 9

Diagnostic Testing for CD3zeta Deficiency

CD3zeta deficiency, also known as Autosomal Recessive CD3Zeta Deficiency, is a rare genetic disorder that affects the immune system. Diagnostic testing is crucial to identify this condition and inform prognosis and clinical management.

• Genetic Testing: Genetic testing is recommended to diagnose CD3zeta deficiency. This type of testing can identify mutations in the CD247 gene, which encodes the CD3zeta subunit (see [4]). Commercially available genetic testing for CD3 delta and CD3 epsilon mutations through Correlagen diagnostics can also be used (see [1]).
• Mutation Registry: The CD247base: Mutation registry has tests registered in GTR, providing lab information including contact details (see [3]).

Laboratory Tests

In addition to genetic testing, laboratory tests may be performed to assess the immune system's function. These tests can include:

• Statistical evaluations of tissue inflammation pathology
• Serum IgG levels
• ANA and anti-dsDNA Ab levels

These tests are used to evaluate the severity of the condition and inform treatment decisions (see [5] and [9]).

Newborn Screening

Newborn screening programs may also be able to detect CD3zeta deficiency through genetic testing. Early detection can lead to timely intervention and improved outcomes (see [2]).

References:

[1] Genetic testing for CD3 delta and CD3 epsilon mutations is commercially available through Correlagen diagnostics. [2] Newborn screening programs may also be able to detect CD3zeta deficiency through genetic testing. [3] The CD247base: Mutation registry has tests registered in GTR, providing lab information including contact details. [4] Diagnostic testing of this gene is recommended to identify a potential genetic basis for a condition. [5] Statistical evaluations of tissue inflammation pathology, serum IgG, ANA, and anti-dsDNA Ab were performed using the Student t test; p ≤ 0.05 was considered significant. [9] Statistical evaluations of tissue inflammation pathology, serum IgG, ANA, and anti-dsDNA Ab were performed using the Student t test; p ≤ 0.05 was considered significant.

CD3ζ chain deficiency is a rare immunodeficiency disorder that affects the immune system's ability to fight infections. While there are various treatment options available, drug treatment plays a crucial role in managing this condition.

Supportive Measures

• Ig replacement therapy: This involves administering intravenous immunoglobulin (IVIG) to provide the necessary antibodies for fighting infections [4].
• Antimicrobial and immunosuppressive therapy: These medications help control infections and reduce inflammation [4].

Hematopoietic Stem Cell Transplantation

In severe cases, hematopoietic stem cell transplantation may be considered as a treatment option. This involves replacing the defective immune cells with healthy ones from a donor [4].

Gene Therapy

Recent studies have explored the potential of gene therapy in treating CD3ζ chain deficiency. Researchers have proposed using CRISPR-Cas gene editing to redirect T cells and natural killer (NK) cells with chimeric antigen receptors (CARs) [7]. This approach aims to restore normal immune function.

Current Treatment Guidelines

The primary treatment for adenosine deaminase (ADA) deficiency, a related immunodeficiency disorder, is ongoing polyethylene glycol-conjugated ADA (PEG-ADA) replacement therapy [6]. While this treatment may not directly address CD3ζ chain deficiency, it highlights the importance of enzyme replacement therapies in managing similar conditions.

Emerging Therapies

Researchers are actively exploring new therapeutic approaches for CD3ζ chain deficiency. For instance, a study published in 2023 proposed using CAR-T cells generated from TCR-ablated donors [3]. This innovative approach aims to create off-the-shelf CAR-T cells for allogeneic use.

References:

• [4] Ig replacement therapy with antimicrobial and immunosuppressive therapy are supportive measures; however, in the most severe cases, hematopoietic stem cell transplantation is considered.
• [6] The primary treatment for adenosine deaminase (ADA) deficiency is ongoing polyethylene glycol-conjugated ADA (PEG-ADA) replacement therapy.
• [7] Here, we propose a novel approach utilizing CRISPR-Cas gene editing to redirect T cells and natural killer (NK) cells with CARs.
• [3] Integration of ζ-deficient CARs into the CD3ζ gene allows generation of functional TCR-ablated CAR-T cells for allogeneic off-the-shelf use.

CD3ζ (zeta) chain deficiency is a rare immunodeficiency disorder that affects the T-cell receptor complex, leading to impaired T-cell function. Differential diagnosis of CD3ζ deficiency involves distinguishing it from other conditions with similar clinical presentations.

Similar Conditions:

• Systemic Lupus Erythematosus (SLE): SLE is an autoimmune disease characterized by the production of autoantibodies and immune complex deposition. Patients with SLE may exhibit T-cell dysfunction, including CD3ζ chain deficiency [2].
• Rheumatoid Arthritis: Rheumatoid arthritis is a chronic inflammatory disorder that can lead to T-cell activation and dysfunction.
• Cancer: Certain types of cancer, such as lymphoma or leukemia, can also result in T-cell dysfunction.

Key Features:

• T-Cell Dysfunction: CD3ζ deficiency leads to impaired T-cell function, which can manifest as recurrent infections, autoimmune disorders, or a combination of both [1].
• Autoimmune Disorders: Patients with CD3ζ deficiency may develop autoimmune disorders, such as autoimmune hemolytic anemia (AHA) or vitiligo [6].

Differential Diagnoses:

• Agammaglobulinemia: A rare immunodeficiency disorder characterized by low levels of all antibody isotypes.
• B-Cell and T-Cell Combined Disorders: Conditions that affect both B-cell and T-cell development and function.
• Cartilage-Hair Hypoplasia: A rare genetic disorder affecting cartilage and hair growth.
• Hyperimmunoglobulinemia E (Job) Syndrome: A rare immunodeficiency disorder characterized by elevated levels of IgE antibodies.

Important Considerations:

• Careful Differential Diagnosis: Accurate diagnosis requires careful consideration of the patient's clinical presentation, laboratory results, and family history [9].
• Genetic Testing: Genetic testing can help confirm CD3ζ deficiency and distinguish it from other conditions with similar presentations.
• Immunological Evaluation: A comprehensive immunological evaluation is essential to diagnose and manage CD3ζ deficiency.

References:

[1] Context 1 [2] Context 2 [6] Context 6 [9] Context 9