The Australasian Society of Clinical Immunology and Allergy

Home

Primary Immune Deficiency Diseases

Primary immune deficiency diseases (PID) are a group of potentially serious disorders in which inherited defects in the immune system lead to increased infections. There are more than 100 separate primary immune deficiency diseases, with new disorders being described regularly.

The ASCIA PID Committee and the ASCIA PID Register provide support to patients and their medical teams.

What are primary immune deficiency diseases?

Although everyone experiences infections of one form or another, some people have infections that seem to fall beyond the scope of normal immune defense. Examples include:

infections that are unusually persistent, recurrent or resistant to treatment
Infections involving unexpected spread or unusual organisms.

Such cases may be explained by inherited defects of the immune system, known as primary immune deficiency diseases (PID). Many of these are rare diseases of childhood, but some emerge for the first time in adulthood.

Being caused by defects in the genes that control the immune system, PID diseases are not related to AIDS (acquired immunodeficiency syndrome) which is due to infection with human immunodeficiency virus (HIV).

What are the warning signs of primary immune deficiency diseases?

Many patients have experienced similar patterns of symptoms. These can be called warning signs and symptoms:

1. Eight or more ear infections within one year
2. Two or more serious sinus infections within one year
3. Two or more months on antibiotics with little effect
4. Two or more pneumonias within one year
5. Failure of an infant to gain weight or grow normally
6. Recurrent deep skin or organ abscesses
7. Persistent thrush in mouth or elsewhere on skin after age one
8. Need for intravenous antibiotics to clear infections
9. Two or more deep-seated infections such as sepsis, meningitis or cellulitis
10 A family history of primary immune deficiency.

What types of primary immune deficiency diseases exist?
PID diseases cause increased susceptibility to infections as well as other problems. For simplicity, these diseases can be categorised into four groups according to what part of the immune system is affected:

1. ANTIBODY DEFICIENCIES

Antibodies are proteins made by specialised white blood cells: B lymphocytes and plasma cells.
The function of antibodies is to recognise infectious agents so that they can be blocked.
Two examples of antibody deficiencies are:

X-linked Agammaglobulinaemia - Infants with this deficiency develop recurrent pus-producing infections of the ears, lungs, sinuses and bones and can get infections in the bloodstream and internal organs. They are also susceptible to certain viruses such as hepatitis and polio. Sometimes this can present in later childhood or adulthood.
Common Variable Immunodeficiency - The most common form of antibody deficiency, usually presenting with recurrent chest and sinus infections in childhood or early adulthood. Early recognition can prevent permanent damage to the lungs called bronchiectasis.

2. COMBINED IMMUNE DEFICIENCIES

T lymphocytes are white blood cells that are critical to a healthy immune system. People who lack T lymphocytes also tend to have weak antibody defences, and this is called "combined" immunodeficiency. Although these are very rare, they are hereditary. The most common is X-linked Severe Combined Immunodeficiency (SCID) - due to a defective gene for T cell growth. Patients are usually diagnosed within the first year of life. These patients will require gene therapy or bone marrow transplantation to survive.

3. COMPLEMENT DEFICIENCIES

The complement system consists of a group of proteins that attach to antibody-coated foreign invaders like bacteria and viruses. Such people may also develop antibodies that react against the body's own cells and tissues. The most common of these deficiencies is C2 Deficiency. This defect can cause an auto-immune disease such as Systemic Lupus Erythematosus (SLE) or can result in severe infections such as meningitis. The illnesses usually appear in childhood or in early adulthood.

4. PHAGOCYTIC CELL DEFICIENCIES

Phagocytes include white blood cells (neutrophils and macrophages) that engulf and kill antibody-coated foreign invaders. Phagocytes can be defective either in their ability to kill pathogens or in their ability to move to the site of an infection. In either case, the defect results in increased infections. The most severe form of phagocytic cell deficiency is Chronic Granulomatous Disease - inherited deficiencies of molecules needed by neutrophils to kill certain infectious organisms. People with chronic granulomatous disease develop frequent and severe infections of the skin, lungs and bones and develop localised, swollen collections of inflamed tissue called granulomas.

Improved therapy can lead to a better and longer life

Research has led to improved therapy for people with primary immune deficiency diseases.
Treatment options include:

I. BONE MARROW TRANSPLANTATION

For patients with combined immune deficiency diseases, transplantation of bone marrow cells from a family member with identical human leukocyte antigens (HLA) can result in normal immune function. 'Tissue typing' of human leukocyte antigens (HLA) greatly decreases the risk of rejection and of graft-versus-host disease.

II. ANTIBIOTICS

The use of antibiotics to treat and prevent infections is a key element in the treatment of primary immune deficiency diseases.

III. IMMUNOMODULATION

Immune system molecules, such as interferon gamma, can be used to improve immune function and reduce infection.

IV. REPLACEMENT OF ANTIBODIES

One of the most effective and most commonly used treatments for PID is to replace antibody levels by using antibodies derived from blood donors.
These can be injected into the vein, (this is known as intravenous immunoglobulin or IVIG) about once a month, or can be administered at home in certain cases using injections under the skin (known as subcutaneous immunoglobulin or SCIG).
These products must be restricted because of shortages in supply.
Doctors need to follow specific guidelines to ensure that the product goes to those most in need.

To ensure future supplies of intravenous human immunoglobulin, people can assist by regularly donating plasma to the Australian Red Cross Blood Service. To find out how, where and when you can donate plasma, phone the Australian Red Cross Blood Service on 13 14 95.

The PID Register of Australia and New Zealand

ASCIA runs an on-line Register of patients with PID. Patient consent is required before entering patient details into the Register. Information on the Register is held under code and anonymity is carefully protected.

ASCIA holds this data to enhance research, therapies and advocacy for these conditions. To achieve this, it is the objective of the ASCIA PID Register to collect data on all patients with PID in Australia and New Zealand.

You can visit the dedicated website at http://www.immunodeficiency.org.au/.

Health professionals who manage patients with PID who have not been entered into the Register should visit the website to determine the steps involved in patient registration.

Please contact This e-mail address is being protected from spam bots, you need JavaScript enabled to view it with queries regarding the PID Register.

The PID Register website also has links to a bioinformatics resource on PID. This contains general information about immunology and PID's, current research in the field and also links to immunology and nurse societies.

Glossary of terms

Antibody
blood proteins which kill germs

B cell (B lymphocyte)
type of lymphocyte or white blood cell which develops into a cell which produces antibodies

Gammaglobulin
part of the blood which contains antibodies

Immunodeficiency
lack of the ability to develop immunity following immunisation or infection

Immunoglobulin
blood proteins which have the function of antibodies

IgG (immunoglobulin G)
main type of antibody

IVIG
a method of enhancing immune defence by replacing missing antibodies, using antibodies derived from the blood donor pool

Stem cell
a type of cell present in bone marrow which has the ability to grow and to form red and white blood cells and platelets

T cell (T lymphocyte)
type of lymphocyte or white blood cell that co-ordinates immunity to infection. Although antibodies are made by B cells, they require the "help" of T cells to do so effectively.

Patient support groups

A number of local and international support groups exist for patients with PID. These are generally run by people who have PID conditions within their families and can be very helpful. Please see the ASCIA website http://www.allergy.org.au/ or
Email: This e-mail address is being protected from spam bots, you need JavaScript enabled to view it for details about patient support groups.

References

http://www.niaid.nih.gov/Publications/pid
Intragam P (CSL) Patient Information Leaflet

Disclaimer

The content of this article has been reviewed by ASCIA members, represents the available published literature at the time of review and is not intended to replace professional medical advice. Any questions regarding a medical diagnosis or treatment should be directed to a medical practitioner.

For further information on allergy, asthma or immune diseases,
visit www.allergy.org.au - the web site of ASCIA.
ASCIA is the peak professional body of Clinical Allergists and
Immunologists in Australia and New Zealand.