Primary Immunodeficiency Diseases

Dr. Ira Shah
Primary Immunodeficiency Diseases - Patient Education
The immune system is the body's defense mechanism to fight against germs and prevent infections in the body. Whenever the body's immune system is overcome, a germ be it a virus or bacteria or fungus can lodge within the body and lead to infection.

A normal healthy individual can also get infections. However, serious repeated infections may suggest that there is something wrong with the child's immune system and that may be leading to repeated serious infections.

Immune system consists of skin, the nose and airway cells and finally various white blood cells (WBCs) in the blood. The skin is the most important barrier for infection. An intact skin prevents entry of most of the germs and any break in the continuity of the skin can lead to infection. Thus, infections are commonly seen in patients with burns.

Our next most common defense mechanism is the airway passages through which we breathe. The air which we breathe may contain plenty of germs and if they were not captured and expelled from the body would lead to different types of infections. The air passages contain a special type of hair called the cilia and also have mucus lining it. Thus any germ is trapped in the mucus and by beating of the cilia is moved upward towards the mouth and expelled out by the cough mechanism. Thus, these 2 most important barriers prevent most of the infections in the human body.

However, if a germ bypasses these 2 defense mechanisms then there are certain cells in the blood (WBCs) that fight these germs. These cells consists of specialized cells called as neutrophils, T lymphocytes, B lymphocytes and monocytes. B lymphocytes also release certain proteins called as antibodies that fight against most of the bacteria. There are 5 major types of antibodies - IgA, IgG, IgE, IgD and IgM. T lymphocytes fight against mainly viruses and fungi.

Thus, any defect in these specialized cells can lead to defective immunity and immune deficiency disorders that may lead to frequent serious infections.

What are primary immunodeficiency diseases (PID)?
When part of the immune system does not function properly, it leads to recurrent infections. The immune deficiency may be inborn and is called primary immunodeficiency. When immune deficiency results due to infection or other acquired causes it is called as secondary immune deficiency. Common causes of secondary immune deficiency are AIDS due to HIV virus, malnutrition, irradiation, burns and chemotherapy.

Which are the common primary immunodeficiency diseases (PID)?
There are over 150 primary immunodeficiency disorders. They may result from defects in T-lymphocytes, B-lymphocytes, NK cells, phagocytic cells or the complement system. (See Immune System)
Common B-lymphocyte or antibody system immunodeficiencies are X-linked agammaglobulinemia (XLA), selective IgA deficiency, IgG subclass deficiency and specific antibody deficiency, common variable immune deficiency (CVID).
T-lymphocyte immunodeficiencies are Wiskott - Aldrich syndrome (WAS), DiGeorge syndrome. Common T & B-lymphocyte immunodeficiencies are severe combined immune deficiency (SCID).
Phagocyte defect commonly seen is chronic granulomatous disease (CGD).
Other common immunodeficiencies are Hyper IgE syndrome, ataxia telangiectasia and complement deficiencies.

Which are less common immunodeficiencies?
- The less common immunodeficiencies are
- Selective IgM deficiency
- Autosomal recessive agammaglobulinemia
- Selective IgE deficiency
- Immunodeficiency with thymoma (Good's syndrome)
- Antibody deficiency with Transcobalamin II Deficiency
- Warts, Hypogammaglobulinemia, Infection, Myelokathexis (WHIM) syndrome
- Chronic Mucocutaneous Candidiasis (CMC)
- Cartilage Hair Hypoplasia (CHH)
- X-linked lymphoproliferative (XLP) syndrome
- X-linked Immune Dysregulation with polyendocrinopathy (IPEX) syndrome
- Interferon- gamma /IL-12 Pathway Deficiencies
- Natural Killer Cell Deficiencies
- Neutropenia
- Specific Granule Deficiency
- Toll-like Receptor (TLRS) Defects
- Mannose-binding lectin (MBL) Deficiency.

How are primary immunodeficiencies inherited?
Many PID are genetic and run in families. X-linked recessive PID such as XLA, WAS, SCID (one form), Hyper IgM (two forms), CGD, (one form) tend to occur in boys. Diseases such as SCID, CGD, ataxia telangiectasia have 25% chance of recurring in other sibling. Some PID occur de-novo.

When is a child suspected to have primary immunodeficiency?
Primary immunodeficiencies are suspected in children with following presentations and secondary immunodeficiencies are not present.
- Recurrent severe infections,
- Infections with an unusual organism
- Infection with a regular organism that takes longer time to heal
- Repeated ear infections or sinus infections.
- More than 2 pneumonias in a year
- Recurrent, deep skin or organ abscesses
- Persistent thrush in mouth after one year of age
- A family history of primary immune deficiency.
- Unusual manifestation of a common infection

How is the diagnosis of primary immunodeficiencies made?
Special laboratory tests are required to diagnose PID. Four major categories of tests are done based on clinical suspicion of which PID is likely in the child. For diagnosis of antibody deficiency, measurement of immunoglobulins IgG, IgA and IgM is done in the blood. Tests to measure specific antibody production are also useful. Measurement of B-lymphocytes (especially CD19 & CD20 cells) is done. For T-cell lymphocyte defects, measurement of specific lymphocytes (CD3, CD4, CD8 is done). For NK cell defects, measurement of CD16 and CD56 is done. Functional capacity of T-cells is tested by T-cell response to mitogens. Neutrophil function is evaluated by determining neutrophil count and measuring neutrophil capability to kill germs (done by Nitroblue Tetrazolium-NBT test). Laboratory evaluation of complement is done by measuring total complement (CH50) or measuring specific complement levels. Genetic tests are done when specific immunodeficiency is diagnosed.

What is the treatment of primary immunodeficiencies?
It is very essential to keep good hygiene and proper nutrition to prevent infections. Goal is to reduce frequency of infections, prevent complications and prevent an acute infection from becoming chronic.

During infections medications to control infection should be started immediately. Specific therapy for specific immunodeficiency is required in form of immunoglobulin therapy for those who are unable to produce adequate amount of antibodies, granulocyte-colony stimulating factor (G-CSF) for patients with neutropenia, gamma-interferon for those with CGD, pegylated-ADA for patients with SCID due to Adenosine deaminase (ADA) enzyme deficiency.

gene therapy and stem cell transplant can be offered in patients with specific genetic defects. Stem cell transplant is often used to cure Wiskott-Aldrich syndrome, Hyper-IgM syndrome, SCID and CGD.

Primary Immunodeficiency Diseases Primary Immunodeficiency Diseases 08/01/2015
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