Types of primary immunodeficiency disease
Common PI diseases include common variable immunodeficiency, X-linked agammaglobulinemia, selective IgA deficiency, DiGeorge syndrome, hypogammaglobulinemia, ataxia telangiectasia, and chronic granulomatous disease
Researchers have identified more than 150 types of
primary immunodeficiency (PI), which can be classified into 1 of 5 categories of immune defect
T-cells, which originate in the bone marrow, are responsible for fighting off viruses and fungi.
A lack of T-cells can lead to frequent infections. One PI disease caused by a T-cell deficiency
is DiGeorge syndrome, a disorder that begins during fetal development and can affect various
parts of the body, including the head, neck, face, parts of the brain, heart, and thymus.
Symptoms of DiGeorge syndrome can be mild to severe, and treatments will vary depending on
whether the immune defect is partial or complete.
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B-cell (antibody) deficiencies
B-cells are the cells that produce antibodies, and more than half of PI diseases are caused by B-cell (antibody) deficiencies. In these types of PI, an individual produces either too few or defective B-cells.
The most common of all PIs, and caused by a B-cell deficiency, is selective IgA deficiency.
In this disease, there is a deficiency of IgA immunoglobulins
in body secretions and the mucous membranes lining the airways and digestive tract.
IgA is normally present at body entrances, fighting off foreign substances. Compared to other PI
diseases, symptoms of selective IgA deficiency tend to be mild and take the form of infections that
are slow to respond to regular antibiotics.
Another common PI caused by B-cell deficiencies is common variable immunodeficiency (CVID),
a form of hypogammaglobulinemia, a condition in which the body doesn’t produce enough immunoglobulins.
Hypogammaglobulinemia can appear in childhood but is typically diagnosed in people in their 20s or
30s. In addition to common bacterial infections, people with this condition can develop other immune
system diseases, such as rheumatoid arthritis, anemia, digestive tract disorders, and even some forms
of cancer. Usually, people with hypogammaglobulinemia receive treatment with
Another PI disease caused by B-cell deficiencies is X-linked agammaglobulinemia (XLA),
which affects only males (females aren’t affected because females have 2 X chromosomes). Males with XLA make no antibodies, and resulting illnesses include bacterial,
viral, and fungal infections that can affect the eye, ear, sinus, and skin and can cause pneumonia.
X-linked agammaglobulinemia can also be treated with immunoglobulin replacement therapy.
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Combined T-cell and B-cell (antibody) deficiencies
Combined deficiencies affect both primary weapons designed to fight germs—B-cells and T-cells.
PI diseases resulting from combined B-cell and T-cell deficiencies include
Wiskott-Aldrich syndrome, X-linked hyper IgM syndrome, ataxia telangiectasia (AT),
and severe combined immunodeficiency (SCID).
Wiskott-Aldrich syndrome is a condition that affects blood cells and the cells of the immune system.
Seen almost exclusively in males, the condition is characterized by a tendency to bleed easily and the
development of an intensely itchy, scaling skin rash (eczema), as well as severe recurrent infections.
Many patients have brothers or uncles with the same disease. The leading treatment option for
Wiskott-Aldrich syndrome is bone marrow transplantation. When bone marrow is available from a sibling
who is an identical match, the cure rate exceeds 85%.
Another PI disease seen almost exclusively in males, X-linked hyper IgM syndrome involves T-cells.
It is characterized by low levels of 3 classes of antibodies: immunoglobulin G (IgG), immunoglobulin A (IgA),
and immunoglobulin E (IgE). The lack of certain antibody classes makes it difficult for people with this
disorder to fight off infections.
Ataxia telangiectasia is a disease that affects several body systems and worsens over time.
Children with ataxia telangiectasia have impaired motor skills, dilated blood vessels in the
eyes and skin, and frequent sinus and respiratory infections. Immunoglobulin replacement therapy
can be given if a patient has an Ig deficiency.
Severe combined immunodeficiency (SCID) is a rare type of PI seen in infants and caused by various
genetic defects. Children with SCID may begin to develop normally, but they soon face frequent,
life-threatening infections. The condition is usually addressed with immunoglobulin replacement
therapy until a bone marrow transplant can be arranged. In a type of SCID in which the enzyme
adenosine deaminase (ADA) is lacking, injections of PEG-ADA will keep away recurrent infections.
SCID is still considered a fatal condition if not treated properly.
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In this type of PI, phagocytes (white blood cells that engulf germs in order to kill them)
do not work properly. One example is chronic granulomatous disease (CGD), a genetic
disease in which phagocytes are unable to make the oxygen-transporting compounds needed to kill
germs. Children with chronic granulomatous disease get frequent infections, lung disease, and
chronic inflammatory conditions. The condition can also cause tumor-like masses called granulomas,
which are white blood cell clusters that accumulate in infected areas after an infection has
disappeared. Children with chronic granulomatous disease are often treated with antibiotic therapy
and/or bone marrow treatments.
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The complement system, an important part of the immune system, consists of more than 20 plasma proteins
that work together as part of the body’s immune response. Genetic changes that produce a deficiency
of a single complement system protein can disrupt the regulation of the complement system. Certain
PI diseases are associated with complement system deficiency.
Fairly rare even among PI diseases, immunodeficiencies involving the complement system might not
appear until adulthood. In some instances, immunoglobulin replacement therapy may be given to boost the
immune system. In addition, researchers have identified complement concentrates to replace or
supplement some complement components; research is ongoing.
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Next: Treatment options for primary immunodeficiency