About Primary Immune Deficiencies<?xml:namespace prefix = o />

Primary immune deficiency diseases occur when part of the body's immune system is missing or does not work properly, often because of genetic defects.  By contrast secondary immune deficiency diseases are seen when the immune system is damaged by other factors such as virus infections or chemotherapy (anti-cancer drugs).

There are a wide variety of primary immune deficiencies.  The World Health Organization recognizes nearly 100 primary immune deficiency disease including X-linked Agammaglobulinemia (Bruton's Disease), Common Variable Immune Deficiency, Selective IgA Deficiency, and Severe Combined Immune Deficiency (boy-in-the-bubble disease).  Some disorders, such as Selective IgA Deficiency can be quite common, occurring as often as 1/500 to 1/1000 individuals. Others, such as Severe Combined Immune Deficiency, may be much rarer, affecting 30-40 babies a year in the <?xml:namespace prefix = st1 />UK. 

Untreated primary immune deficiencies allow frequent life-threatening infections and debilitating illness.  Because of advances in our medical understanding and treatment of primary immune deficiency diseases, individuals who in the past would not have survived childhood are now able to live nearly normal lives. 

Many individuals affected by primary immune deficiency diseases require life long therapies including intravenous gamma globulin infusions, antibiotic therapies, whilst others can be cured by haemopoietic stem cell transplantation (HSCT). 

The Bubble Foundation is dedicated to supporting children with primary immune deficiencies and to improving the diagnosis and treatment of primary immune deficiency diseases through research and education.

Antibody Deficiency

The most common subgroup of conditions.  The immune system fails to produce sufficient antibodies to fight bacterial infections, particularly chest, sinus and ear infections.  The conditions include Common Variable Immunodeficiency (CVI), which can affect both sexes, and X-Linked Agammaglobulimaemia and Hyper-IgM Syndrome - which follow a sex linked pattern of inheritance and usually affects only males.

Ataxia – Telangiectasia

A primary immune deficiency disease that affects a number of different organs in the body. Patients with Ataxia-Telangiectasia have an unsteady gait (Ataxia), dilated blood vessels (Telangiectasia), and a variable immunodeficiency involving both B-lymphocytes and T-lymphocytes.

The first presenting symptom is generally ataxia, a medical term used to describe an unsteady gait.  Another clinical feature of AT is an increased susceptibility to infections.

This symptom is a major feature in some individuals.  Infections most commonly involve the lungs and sinuses, and are usually caused by bacteria or viruses.

Chronic Granulomatous Disease (CGD)

Caused by abnormalities in the neutrophil white blood cells.  People with CGD are susceptible to infections of the lymph glands, chest and skin, which can develop in abscesses.  They are also very susceptible to fungal infections.  A genetically determined (inherited) disease characterized by an inability of the body’s phagocytic cells to kill certain microorganisms.  As a result of this defect in phagocytic cell killing, patients with CGD have an increased susceptibility to infections caused by certain bacteria and fungi.

Children with Chronic Granulomatous Disease (CGD) are usually healthy at birth.  However, sometime in their first few months or years of life, they develop recurrent infections, infections that are difficult to treat, or infections that are caused by unusual organisms such as fungi. The infections may involve any organ system or tissue of the body, but the skin, lungs, lymph nodes, liver, or bones are the usual sites of infection.  Treatment with lifelong antibiotics is helpful; more recently many patients have been cured by HSCT.

Common Variable Immunodeficiency

Common Variable Immunodeficiency (CVID) is a disorder characterized by low levels of serum immunoglobulins (antibodies) and an increased susceptibility to infections.  The exact cause of the low levels of serum immunoglobulins is usually not known.  It is a relatively common form of immunodeficiency, hence, the word “common”. Characteristics include recurrent infections involving the ears, sinuses, nose, bronchi and lungs.

Complement Deficiency

A subgroup of conditions associated with deficiencies in a group of proteins that help the neutrophils to engulf bacteria.  Characteristics of these conditions include meningitis and disorders of the kidneys, joints and skin.

DiGeorge Syndrome

A condition in which the thymus gland (which helps in the development of T-cells) is missing. Symptoms include viral and fungal infections.  These are associated heart defects and muscular spasms caused by low level of calcium in the body.  Learning difficulties are also common.  Affected children can display some of the following characteristics:

Facial appearance - an upward bowing of their mouth, an underdeveloped chin, eyes that slant somewhat downward, low set ears and defective upper portions of their ear lobes. These facial characteristics vary greatly from child to child and may not be very prominent in many affected children.

Underdeveloped parathyroid gland abnormalities.  The parathyroids are small glands found in the neck near the thyroid gland.  They function to control the normal metabolism and blood levels of calcium.  Children may have trouble maintaining normal levels of calcium, and this may cause them to have seizures (convulsions).

Heart defects - affected children may have a variety of heart defects. For the most part, these anomalies involve the aorta and the part of the heart from which the aorta develops.

Thymus gland abnormalities – affected infants and children may have abnormalities of their thymus.

In addition to the above features, patients with the DiGeorge Syndrome may occasionally have a variety of other developmental abnormalities including cleft palate, poor function of the palate, delayed acquisition of speech and difficulty in feeding and swallowing.  Also, some patients have learning disabilities and hyperactivity.

IgG Subclass Deficiency

There are five classes of immunoglobulins: IgG, IgA, IgM, IgD, and IgE.  The IgG class of immunoglobulins is itself composed of four different subtypes of IgG molecules called the IgG subclasses.  Patients who lack, or have very low levels of, one or two IgG subclasses, but whose other immunoglobulin levels are normal, are said to have a selective IgG subclass deficiency.  Some patients are hardly troubled by infections at all, whereas others suffer recurrent ear infections, sinusitis, bronchitis and pneumonia, which are the most frequently observed illnesses in patients with IgG subclass deficiencies.  Both males and

females may be affected.

Neutropenia

Caused by reduction in the numbers of neutrophils, the "scavenging" cells that kill most micro-organisms that enter the body.  Symptoms include skin and lung infections, ulcers and septicaemia.

Selective IgA Deficiency

Individuals with Selective IgA Deficiency are deficient in IgA but usually have normal amounts of the other types of immunoglobulins.  Selective IgA Deficiency is the most common of the primary immunodeficiency diseases.  Patients with Selective IgA Deficiency may have very variable symptoms.  Some IgA deficient patients may be relatively well with very mild, if any, clinical illnesses while others may be affected by a variety of infections, particularly of chest and gut.

Severe Combined Immunodeficiency (SCID)

The most serious of all the conditions, caused by the failure of both the T-cell and B-cell systems that fight infections and make antibodies.  SCID is characterised by severe infections.  It is caused by a number of different genetic defects.  These defects lead to extreme susceptibility to infection.  This condition is generally considered to be the most serious of the primary immunodeficiencies.

Infants with SCID develop severe and persistent infections in the first few months of life. However, the infections are not usually the same types of infections that normal children have, e.g., frequent colds.  The infections in patients with SCID can be much more serious and even life-threatening.  These may include pneumonia, meningitis or bloodstream infections.  Treatment with HSCT can be difficult and so should be carried out in a specialist centre that treats SCID babies all the time; however, results are now good and most babies can be cured and lead normal or near normal lives.

Wiskott-Aldrich Syndrome

A complex condition characterised by infections of the ear, sinus and chest; spontaneous bleeding and bruising; and eczema.  The genetic abnormality at the root of this condition has recently been defined and affects all parts of the immune system, as well as the blood cells called platelets that help control bleeding.

The clinical presentation of the Wiskott-Aldrich Syndrome (WAS) varies from patient to patient.  Some patients present with all three classic manifestations, including low platelets and bleeding, immunodeficiency and infection, and eczema.  Other patients present just with low platelet counts (thrombocytopenia) and bleeding.

The X-Linked Hyper IgM Syndrome (CD40 Ligand deficiency)

Patients with the X-linked Hyper IgM Syndrome have a deficiency of a protein, CD40 ligand, which is found on the surface of T-lymphocytes.  As a consequence of the deficiency of this protein, their T-lymphocytes are unable to instruct B lymphocytes to switch their production of immunoglobulins from IgM to IgG and IgA.  As a result, patients have decreased levels of IgG and IgA and normal or elevated levels of IgM.  In addition, since CD40 ligand is important to other functions of T-lymphocytes, they also have a defect in some of the protective functions of their T-lymphocytes.

Most patients with the X-linked Hyper IgM (XHIGM) syndrome develop clinical symptoms

during their first year or second year of life.  Their most common problem is an increased susceptibility to infection.  The most common infections are recurrent upper and lower respiratory tract infections.  HSCT is being increasingly used to cure patients with CD40 Ligand deficiency.