Immune Deficiency Disorders (Pediatric)

What are immune deficiency disorders?

The immune system is a network of highly specialized blood cells and other mechanisms in the body that fight off disease, whether it be infections from bacteria or viruses or illnesses that originate from within the body, such as cancer.

Immune deficiency (or “immunodeficiency”) is the term for any of a number of conditions in immune system loses part or all of its ability to fight infectious disease. In some cases, immune deficiency can also affect the body’s ability to perform its natural function of attacking cells that may become cancerous.

A person who has an immunodeficiency of any kind is said to be immunocompromised.

An immunocompromised person may be particularly vulnerable to opportunistic infections, such as fungal and viral disorders as well as normal infections that could affect everyone.

Some people are born with defects in their immune system, which is called “primary” immunodeficiency. Most cases of immunodeficiency are acquired (“secondary”), meaning they are not conditions the patient was born with, but were caused by an illness or toxin later on.

Primary immunodeficiency

Primary immunodeficiencies involve defects within the immune system itself. Many of the conditions that cause immunodeficiency are rare diseases passed along from one or both parents. There are over 80 recognized primary immunodeficiency conditions; they are generally labeled by the part of the immune system that is not working. Examples include:

• Humoral immune deficiency is associated with a condition called “hypogammaglobulinemia,” in which the body does not make enough of certain important kinds of antibody. A common symptom of his disorder is repeated respiratory infections.
• Cell-mediated immune deficiency, including T-cell immune deficiencyDefects in immune cell structures, such as T-cells can leave the patient vulnerable many infections that do not affect people with normal immune function¹ Lack of T-cell can result from hereditary conditions such as severe immune combined deficiency (SCID). Partial T-cell function occurs in conditions such as acquired immune deficiency syndrome (AIDS) and genetic conditions such as DiGeorge Syndrome, Ataxia Telangiectasia and Wiskott Aldrich syndrome.
• Granulocyte deficiencies include low numbers or absence of immune cells called granulocytes, which perform an important job of attacking bacteria²Granulocyte disorders also include decreased function of individual granulocytes, such as in chronic granulomatous disease
• Asplenia, where there is no function of the spleen, which helps fight infection as a key part of the body’s lymph system
• Complement disorders are a deficiency the complement system, which is a group of proteins in the blood that typically help white blood cells fight infection³

Most immunodeficiency syndromes affect multiple systems and are not isolated to just one part of the immune system. Examples include SCID, which is primary, and AIDS, which is secondary.

Secondary immunodeficiencies

Secondary immunodeficiencies, also known as acquired immunodeficiencies, can be the result of using various medications, such as chemotherapy or environmental toxins that suppress the action of the immune system (these substances are said to be “immunosuppressive”), malnutrition, aging and medications such as chemotherapy, immunosuppressive drugs after organ transplants, and glucocorticoids.

For medications, the term immunosuppression generally refers to both beneficial and potential adverse effects of decreasing the function of the immune system, while the term immunodeficiency generally refers only to the adverse effect of increased risk for infection.

Our approach to immune deficiency disorders

Initial testing in patients with suspected immune deficiencies includes a complete blood count, a measurement of the different types of blood cells in the blood and how many there are; immunoglobulin measurements and antibody titers, both of which are measures for types of antibodies in the blood; and skin testing for delayed hypersensitivity, another type of immune reaction. Additional testing is indicated if these initial tests suggest a specific disorder of immune cell or complement function. These can include additional testing of blood, cells, and genetic testing for specific mutations.

Treatments usually involve managing any infections that are already present and preventing future infection, and replacing or boosting the parts of the immune system that are damaged or missing. Therapies may include stem cell transplantation and gene therapy.

Treatment for primary immunodeficiencies:

The treatment of primary immunodeficiencies depends on the nature of the disorder, and may involve infusions of antibodies to boost the immune system, long-term antibiotics, and in some cases, stem cell transplantation.

Treatment of primary immunodeficiencies may also utilize some of the treatments for secondary immunodeficiencies discussed below.

Treatment for secondary immunodeficiencies:

Many specific diseases directly or indirectly cause immunodeficiency such as cancer, particularly leukemia, lymphoma and certain chronic infections.

Immunodeficiency is also the hallmark of acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV). HIV directly infects a small number of T helper cells, and also impairs other immune system responses indirectly.

There are a large number of immunodeficiency syndromes that can autoimmunity, in which the immune system is known to attack the cells and tissues of the patient’s own body. The decreased ability of the immune system to clear infections in these patients may be responsible for causing autoimmunity by causing the immune system to be active all the time, even if it isn’t working properly.

Examples of autoimmune conditions include inflammatory bowel disease, autoimmune thrombocytopenia (a bleeding disorder), autoimmune thyroid disease (which affects the body’s hormonal system) and familial hemophagocytic lymphohistiocytosis (an inherited condition that causes certain immune cells to grow out of control).

Therapy for these conditions is directed at removing the cause of the disorder, managing symptoms, treating infections, and managing each condition with the appropriate therapies.