Dr Ira Shah
Consultant Pediatrician, Nanavati Hospital and B.J.Wadia Hospital for Children, Mumbai
Editor - Pediatric Oncall

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

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.

Last updated on 26-3-2011