Primary Immunodeficiency Diseases

Dr. Ira Shah
Consultant Pediatrician, Nanavati Hospital and B.J.Wadia Hospital for Children, Mumbai, India.
First Created: 04/02/2002  Last Updated: 08/01/2015

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.

The 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 to 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 a mucus lining it. Thus any germ is trapped in the mucus and by the 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 consist of specialized cells called neutrophils, T lymphocytes, B lymphocytes, and monocytes. B lymphocytes also release certain proteins called 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 secondary immune deficiency. Common causes of secondary immune deficiency are AIDS due to the 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 is commonly seen in 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 PIDs are genetic and run in families. X-linked recessive PID such as XLA, WAS, SCID (one form), Hyper IgM (two forms), CGD, (one form) tends to occur in boys. Diseases such as SCID, CGD, ataxia-telangiectasia have a 25% chance of recurring in other siblings. Some PID occurs de-novo.

When is a child suspected to have primary immunodeficiency?

Primary immunodeficiencies are suspected in children with the 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, the measurement of specific lymphocytes (CD3, CD4, CD8 is done). For NK cell defects, the measurement of CD16 and CD56 is done. The 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. The goal is to reduce the 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 an 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 2015-08-01
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