Immune deficiency

Why do people with A-T suffer from immune deficiency?

A large proportion (60-80%) of people with Ataxia-Telangiectasia (A-T) have an impaired immune system (immunodeficiency) and are troubled with recurrent or severe infections. This immunodeficiency is variable with some individuals significantly affected and others not at all. Those affected are particularly at risk of repeated chest, ear and sinus infections which if unchecked may contribute to permanent damage to these organs.

We don’t yet fully understand the mechanism of the immunodeficiency but we do know that several parts of the immune system are involved. There are at least two aspects of the immune system that are likely to be affected by a lack of ATM protein.

The first involves antibodies (also known as immunoglobulins) and specific white blood cells (T and B lymphocytes) that can recognise and fight germs. During the process of creating these, certain parts of the DNA in the immune cells need to be rearranged. This involves breaking up and then repairing the DNA in a slightly different pattern. It is this process that allows the development of diversity in the immune system to enable it to respond to the numerous different bugs the body may encounter.

Now we know that ATM protein is involved in DNA repair. It is therefore likely that this process is impaired in people with A-T.

Secondly, we know that the normal function of the thymus gland depends on ATM. The thymus gland lies within the chest and is essential for the development of T cells. T cells are necessary for fighting infections and in the co-ordination of the immune system. It is likely therefore that impairment of the thymus gland also contributes to the immunodeficiency.

How is the immune system affected?

T-Lymphocyte deficiencies

A-T patients may have deficiencies in their T-lymphocytes. Since these cells make up the majority of blood lymphocytes this will cause a low total lymphocyte count which can be picked up on a simple full blood count test. Other tests looking at the ability of T lymphocytes to multiply in response to a stimulus may also be abnormal.

If this is present then affected children may be less well able to handle virus infections such as chicken pox or measles. Fortunately, for reasons which we do not fully understand certain other types of infection (for example pneumonia due to a germ called Pneumocystis Cariini) which are a particular problem in children with T-lymphocyte deficiency due to other medical conditions, do not seem to be a problem in A-T patients.

Antibody deficiencies

There are a variety of classes of antibodies but the most common deficiencies in A-T are:

IgA         The commonest abnormality found is deficiency of immunoglobulin A (IgA). This is the main antibody produced in the secretions in the respiratory tract, mouth and intestines and is therefore important in protecting these areas from infection.

IgG2       Deficiency of IgG2 is relatively common in A-T patients and often goes with IgA deficiency. IgG2 is the particular sub-type which is important in the responses to certain bacteria which are important causes of chest, ear and more serious infections.  These bacteria include a germ called Pneumococcus and also Haemophilus influenzae type b (known as 'Hib', for short).

Treating immunological problems

In view of this, it is important that everyone with A-T is reviewed by a doctor who understands the immune system (an Immunologist). Blood tests can be taken to check the different parts of the immune system and in some cases, the doctor may prescribe regular antibiotics over the long term to protect against infection. Extra doses of vaccines may also be recommended to maximise immunity to common germs. In the more severe cases (about 10-15% of people with A-T) there is a need for regular antibody (immunoglobulin) injections (immunoglobulin replacement therapy) to prevent frequent infections. You can find out more about the best way to treat immunological problems in our clinical guidance document.

Howard Lederman talks at the Clinical Research Conference

In this video, Dr Howard Lederman of the Johns Hopkins A-T Center in the USA discusses the immunological features of A-T.

 

 

Two technicians work on a sample from an A-T patient in the Queen's Medical Centre Nottingham.

The immunology lab for the A-T Centre in Nottingham.