Primary Immunodeficiency

Primary cellular immunodeficiencies (PID) are a group of inherited disorders characterized by severe impairment of the immune systems in the body, which generally leads to early death from infectious complications. Mainly T lymphocytes, B lymphocytes and Natural Killer cells play a pivotal role for immune system, whereas neutrophils and other phagocytes play a role in primary defence.

To be considered a primary immunodeficiency, the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood.

What Causes Primary Immune Deficiency Disease?

While not contagious, these diseases are caused by hereditary or genetic defects, and, although most disorders present at birth or in early childhood, the disorders can affect anyone, regardless of age or gender. However, certain varieties affect the male child only. Some affect a single part of the immune system; others may affect one or more components of the system.

While the diseases may differ depending on type and person to person, they all share one common feature: each results from a defect in one of the functions of the body's normal immune system and results in severe and recurrent infections. The symptoms are usually in the form of:

• Frequent and recurrent pneumonia
• Bronchitis
• Sinus infections
• Ear infections
• Meningitis
• Skin infections and blood infections

In addition to frequent infections, other problems that may occur include: Abnormalities in nails, skin and bones; Inflammation and infection of internal organs; Blood disorders, such as low platelet counts or anemia; Digestive problems; Delayed growth and development; Autoimmune disorders.

Classification of Primary Immune Deficiency Disease

Unlike cancers, diagnostic criteria and conditioning for PID diseases is often more complex. Common diseases include:

SEVERE COMBINED IMMUNE DEFICIENCY (SCID) is caused by a group of genetic disorders with a shared phenotype of deficient or absent T lymphocyte function. Unless the immune system is restored by Allogeneic BMT, children with SCID generally die of infections during the first year of life.

COMMON VARIABLE IMMUNE DEFICIENCY (CVID) is a disorder characterised by abnormality in B cells resulting in decreased or absent levels of immunoglobulins (IgG, IgA, IgM). Patients are highly susceptible to infections of the ears, sinuses, and lungs.

Other diseases include syndromes with T-cell defects such as Wiskott–Aldrich Syndrome (WAS) and Hyper IGM1 Syndrome, and inherited predispositions to Hemophagocytic Lymphohistiocytosis (HLH).

Complete Blood Count: A careful examination of routine blood count often gives an indication by reduced lymphocyte or neutrophil counts.

Flow Cytometry: This is the key test to determine the presence or absence or reduction in various immune cells. This also looks for specific marker proteins like WASP, Perforin, SAP, XIAP which are absent in particular syndromes.

Quantitative Immunoglobulins: A measure of various immunoglobulin levels. This is done to detect abnormalities in the B lymphocytes.

Cytogenetics: Done to find out the abnormalities in the chromosomes.

Antenatal Screening: For mothers who have already had a child with a PID, prenatal testing can be done through Chorionic Villus Sampling or Amniocentesis.

Complications

• Recurrent infections
• Autoimmune disorders
• Damage to heart, lungs, nervous system or digestive tract
• Slowed growth
• Increased risk of cancer
• Death from serious infection

Definitive cure is generally only achieved by ALLOGENEIC BMT, though recent advances in gene therapy hold significant promise.

When is BMT needed? As soon as it is diagnosed — several studies have demonstrated that infants transplanted at less than 3.5 months of age have improved survival. This is likely due to development of pulmonary infections prior to transplant.

Conditioning: Few cases don't need conditioning. Otherwise Reduced Intensity Conditioning with low doses of chemotherapy or radiation is the preferred option.

Donor: Although we prefer a matched family donor, a Half Matched (Haploidentical) family donor or a Matched Unrelated donor provide excellent survival.