Primary immunodeficiency

The immune system is composed of a variety of cells, especially white blood cells, and proteins, for which one of the principal functions is microbial defense. A deficit in the immune system can therefore lead to unusually severe or uncommon recurrent infections. Immune deficits (immunodeficiency) may be primary or secondary. Primary immunodeficiencies, often genetic, are caused by problems in the formation of the immune system itself and not by external factors.

How does a primary immunodeficiency present?

One must suspect an immune deficit in the context of infections that are recurrent, atypical, severe, or that do not respond well to standard treatments. A family history or growth delay and failure to thrive in the infant may also lead to this diagnosis.

What are the types of immunodeficiency?

Even though these are relatively rare disorders, primary immune deficiencies are numerous. They are generally classified 4 ways:

• Antibody deficiency: antibodies are proteins that attach to microorganisms that attack us. People with this type of problem often have respiratory problems (sinusitis, pneumonia, otitis) but can also present with meningitis, septicemia (blood infection) and gastrointestinal infections.
• Cellular or combined deficiencies: Lymphocytes, types of white blood cells that protect the body from microbes are absent or dysfunctional. This type of immune deficiency, often severe, is typically diagnosed in the young baby that presents with several severe or atypical infections. It can also be accompanied by various problems affecting different parts of the body.
• Disorders in phagocytosis: Certain white blood cells are responsible for phagocytosis, that is to say, they are capable of "eating" microbes. A deficit in this function can lead to recurrent skin infections, abscesses, with involvement of lymph nodes, lungs, bones...
• Disorders in complement: Complement proteins play a diverse role in the immune defense. A problem at this level can cause meningitis, respiratory infections, and auto-immune disease.

Auto-immune diseases may affect many different organ systems (such as lupus), or a single system (ex: thyroid, blood cells, kidneys, joints). A deficiency of a protein belonging to the complement system can also cause recurrent episodes of swelling (angioedema), but this pathology will not be discussed in this section.

How does one diagnose an immunodeficiency?

The diagnosis is suspected by history. Following this, very specific testing might be ordered by the allergist-immunologist. Sometimes the tests are sent to specialised centres. It is important to test for the number and function of certain cells (ex: white blood cells) and proteins (ex: antibodies and complement proteins) in the blood. It is possible that the doctor will also radiological tests or genetic tests.

Can an immunodeficiency be cured?

Since the majority of primary immune deficiencies are caused by problems at the level of the gene, they do not resolve spontaneously. However, certain treatments can lead to improvement.

How does one treat an immunodeficiency?

The treatment depends on the type of immune deficiency. First of all, the patient must be followed by an allergist-immunologist to ensure that complications are treated rapidly. The doctor will offer advice regarding prevention of infection, and general measures to take, including vaccination. In certain immune disorders, particular vaccines, predominantly those containing live vaccines, may be dangerous.

Infections can be controlled or rapidly treated using antibiotics. When antibodies are absent, low or dysfunctional, they may be replaced using antibody solutions called immunologlobulins or gammaglobulins. Replacement immunoglobulins are pooled from multiple donors and can be administered either intravenously or subcutaneously. Other medications exist for specific immune deficits. For certain types of immune deficiencies, the doctor may recommend a bone marrow transplant. The bone marrow is the site of production of cells for the immune system, and so the patient's deficient immune system is essentially replaced by another one given by a donor. Other treatments, such as gene therapy, are under study in specialised centres.

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Nha Uyen Nguyen-Luu, MD FRCPC
Hugo Chapdelaine, MD FRCPC
(translation: Andrew Moore, MD FRCPC)