Primary T-Cell Immunodeficiency: Signs, Types, and Care

Primary T-cell immunodeficiency is a group of rare primary immunodeficiency (PI) disorders that make it harder for the immune system to fight infections. These conditions mainly affect T cells — a type of white blood cell that helps find and destroy infected or abnormal cells. In primary T-cell immunodeficiency, T cells may not develop correctly or work as they should, resulting in frequent or severe infections that are harder to treat.

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In babies and children, this condition can also cause failure to thrive, which means that a child isn’t growing or reaching developmental milestones as expected for their age.

In this article, we’ll explore the signs and types of primary T-cell immunodeficiency and discuss treatment options.

What Is Primary T-Cell Immunodeficiency?

Primary T-cell immunodeficiencies are genetic disorders (inherited conditions) caused by mutations (changes) in certain genes. These mutations can result in T cells that are missing, too few in number, or unable to work properly, making it hard for the body to fight infections.

T cells are a type of white blood cell known as lymphocytes, which are a key part of the immune system. There are two main types of lymphocytes — B cells and T cells. T cells get their name from the thymus — a small immune system organ in the chest where they mature.

B cells help fight infection by making proteins called antibodies, which help the immune system recognize and destroy harmful germs.

T cells have several roles:

• Helper T cells support B cells and activate other immune cells.
• Cytotoxic T cells attack and destroy tumor cells and cells infected with harmful bacteria or viruses.
• Regulatory T cells help balance the immune system by turning off other T cells that are no longer needed.

When T-cell levels are too low (a condition called T-cell deficiency), the immune system can’t respond effectively to infections. That means that people with a T-cell deficiency are more likely to get serious infections.

What Are the Signs of Primary T-Cell Immunodeficiency?

Babies with primary T-cell immunodeficiency often show signs of the condition within the first few months after birth. Because T cells are crucial for fighting infections, these babies may develop frequent, severe infections that don’t improve with standard treatments. They may also get infections that usually don’t affect people with a healthy immune system.

Early signs of primary T-cell immunodeficiency may include:

• Diarrhea
• Thrush (white patches in the mouth or throat)
• Poor growth or weight gain

Some types of primary T-cell immunodeficiency can affect other parts of the body, leading to:

• Heart problems
• Low calcium levels in the blood
• Cleft palate (an opening in the roof of the mouth that forms before birth)
• Rashes and other skin problems
• Blood vessel problems

Newborn screening done a day or two after birth can often detect T-cell deficiencies before other signs and symptoms appear.

What Are Some Types of Primary T-Cell Immunodeficiency?

There are several types of primary T-cell immunodeficiency, each caused by a different genetic mutation. Below are some of the more common types.

Severe Combined Immune Deficiency

People born with severe combined immune deficiency (SCID) have no T cells. SCID is one of the most severe forms of PI and is life-threatening without treatment. The main sign is serious, difficult-to-treat infections.

More than 20 different genetic changes can cause SCID. Some types also affect B cells, leaving a person without a functioning immune system. Without treatment, most babies with SCID don’t live past age 2.

DiGeorge Syndrome

DiGeorge syndrome (also called 22q11.2 deletion syndrome) is most commonly caused by a missing piece on chromosome 22. This genetic change affects how the thymus and other organs develop. As a result, the thymus gland may be small or even absent, preventing T cells from developing normally.

Along with a weakened immune system, people with DiGeorge syndrome may have:

• Heart problems
• Low calcium levels
• Ear or eye problems
• Cleft palate
• Autoimmune disease
• Learning or behavioral differences

Ataxia-Telangiectasia

Ataxia-telangiectasia (A-T) is a rare type of PI caused by a defect in the body’s ability to repair DNA damage. The chromosomes may develop abnormal changes and breaks more often, which can have harmful effects. Because of these defects, A-T is classified as a DNA breakage syndrome. It affects multiple parts of the body, including the immune system and nervous system.

People with A-T often have both B-cell and T-cell immunodeficiency, making them more prone to infections, especially in the lungs or sinuses. Other A-T symptoms include:

• Ataxia (uncoordinated movements that make walking difficult)
• Telangiectasia (abnormally widened blood vessels) in the whites of the eyes or on sun-exposed skin
• Difficulty speaking
• Increased risk of cancer

Idiopathic T-Cell Lymphopenia

If healthcare providers aren’t sure why a T-cell immunodeficiency occurred, they may call it idiopathic T-cell lymphopenia — meaning the cause is unknown. In some cases, genetic testing can help identify the reason. However, not all genetic changes that cause PI are known. Reanalyzing genetic test results every few years can help if you don’t have an exact diagnosis.

How Are Primary T-Cell Immunodeficiencies Diagnosed?

Diagnosing primary T-cell immunodeficiency often involves several steps. Newborn screening tests can check for PI disorders involving T cells right after birth. Additional tests can help confirm a diagnosis or find the underlying cause of the immune problem.

Newborn Screening

Newborn screening tests can allow for early diagnosis of many primary T-cell immunodeficiencies. A healthcare provider takes a small sample of blood one to two days after birth. A special machine measures the blood sample’s amount of T-cell receptor excision circles (TRECs) — small pieces of DNA normally cut out of T cells as they mature in the thymus. The number of TRECs indicates how many T cells are in the blood.

An abnormal TREC result may mean the baby has a T-cell deficiency, and more testing is needed. Between 40 percent and 50 percent of babies with an abnormal TREC result are found to have a T-cell deficiency. Some other medical conditions that can cause T-cell deficiency include:

• Birth defects affecting the heart or digestive tract
• Premature birth, especially very early
• Lymphatic system diseases
• Medications taken by the mother during pregnancy or exposure to certain viruses
• Down syndrome
• Leukemia
• Human immunodeficiency virus (HIV) infection

Additional Testing

People with abnormal TREC results are referred to an immunologist — a doctor who specializes in diseases of the immune system. The immunologist may order more tests to help determine if T-cell deficiency is caused by PI or another condition.

Testing may start with immunophenotyping, which counts the number of T cells and other immune cells directly. This test also examines the cells’ phenotypes — specific traits or behaviors — to help identify the type of cell involved. Additional blood work and genetic testing can help the immunologist pinpoint the cause of T-cell deficiency.

How Is Primary T-Cell Immunodeficiency Treated?

Everyone with PI should take special precautions to avoid infections, and in some cases, temporary isolation may be necessary. Early diagnosis and treatment can help reduce both the number and severity of infections. Specific treatments depend on the type of primary T-cell immunodeficiency and may include:

• Immunoglobulin replacement therapy — Provides antibodies to help fight infections
• Hematopoietic stem cell transplant (HSCT) — Replaces dysfunctional blood-forming cells through a bone marrow transplant
• Enzyme replacement therapy — Replaces a missing or defective enzyme (protein), such as in adenosine deaminase SCID
• Gene therapy — Replaces the faulty PI-causing gene (a treatment currently available only in clinical trials)
• Thymus transplant — Transplants donor thymus gland tissue into someone without a thymus (such as in DiGeorge syndrome)

Procedures such as HSCT and thymus transplant can sometimes allow people with primary T-cell immunodeficiency to lead healthy lives. Your healthcare team can help determine which treatment options are best for your situation.

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