Immunity

Immunodeficiency

We have worked hard to try to ensure that the information in this leaflet is accurate and we have referred to many experts in the field of immunology. These include Dr Kathleen Sullivan of the Children's Hospital of Philadelphia, USA; Dr Philip Wood, Consultant Immunologist, St James' Hopsital, Leeds, Professor Gow, Research Scientist, Aberdeen University; and Dr D S Kumararatne, Consultant Immunologist, Addenbrooke's Hospital, Cambridge. The leaflet has been reviewed and is supported by Dr Andrew Gennery of the Great North Childrens' Hospital, Newcastle upon Tyne.

The immune system is one of the most complicated systems in the body. We are very happy to provide whatever support we can but please ask your own doctor for advice if you have any specific queries regarding your child's immunity.

How the Immune System works

To understand how your child's immune system can be affected it's helpful to have a brief look at how a normal immune system works.

A normal immune system is made up of a complex mixture of white blood cells and proteins that work together to fight invading germs such as viruses, fungi and bacteria.

Recurrent infections will occur if the immune system is missing one of its components. If this happens the person is said to be immunodeficient. How badly someone is affected will depend on which cells or proteins are affected, whether they are missing altogether, present in low numbers or unable to function properly.

Some of the white cells can rush in and 'gobble up' certain germs as soon as they enter the body. Other white cells plan a long-term strategy. Once they have been exposed to a germ they will remember having met it before and react more effectively the next time they encounter it.

The white blood cells that have a memory are called lymphocytes. These are divided into two major groups, the B and T cells. Under the microscope they look alike but their functions are very different:
  • If there are only low levels of Tc (CD8) cells viral infections can be slow to clear.
  • With only a few Th (CD4) cells the B cells will not get all the help they need to produce plenty of immunoglobulins. Antibody levels will be low and so recurrent bacterial infections are likely to be a major problem. People with DiGeorge syndrome often suffer from repeated attacks of the same infection.
  • Fungal infections, especially thrush caused by the yeast, candida, are a major risk if the T cell levels are reduced. Recurrent or severe thrush is an indicator of poor T cell function. If the candida infection becomes deep seated within the body it is an extremely severe infection.

The effect of a 22q11.2 deletion

The 22q11.2 deletion may affect the development of the thymus gland during pregnancy. The thymus is a small gland that can be seen as a shadow on
x-ray, at the base of the neck.

Children with the deletion may have a very small thymus, it may be found somewhere other than the base of the neck, it may not work effectively or occasionally it may be completely absent.

Without a fully functioning thymus children are unable to produce normal numbers of T cells. Very rarely the cells that are made are unable to work efficiently.

Some children may not have a thymic shadow on X-ray but do have a good immune system. This is because as the baby developed, a small cluster of thymus cells ended up somewhere else in the body, but this is sometimes sufficient to help the T cells mature normally.

Only a very small proportion of children with a 22q11.2 deletion have seriously reduced or absent T cells, but many more have lower than normal levels of T cells
The infections most likely to occur are:
  • Chest infections, often recurrent pneumonia.
  • Ear infections, frequent otitis media (glue ear) leading to the insertion of grommets.
  • Diarrhoea and vomiting
  • Eye infections.

Chicken Pox

This is an infection that deserves a special mention. For most people it is just one of those childhood infections that many people blithely claim is best to catch early to 'get it over with'!

Unfortunately the chickenpox and other herpes viruses (e.g. the one that causes cold sores) can prove to be very serious infections in babies and other people with a poorly functioning immune system. It is important to make people around you aware of this so that infections are not passed on to a susceptible child.Some children may be offered vaccination if their immune system is developed enough to respond to it.

If your child has been exposed to chicken pox a blood test can confirm that they are not immune to the disease. This can be requested from your GP (who may refer you to your nearest paediatric Hospital A&E department) or your child's Paediatrician. Treatment with specific anti-chicken pox antibodies may be given but these are in very short supply and might be unobtainable. Anti-viral therapy might also be appropriate.
These should NOT be given to immunodeficient patients except under expert advice taking into consideration the development of the individual child's immune system.

Blood tests

Not all children will need to have the full battery of tests carried out but others will be done as a matter of routine.

Full Blood Count - This is the first test that must be done as soon as a 22q11.2 deletion is suspected, and it can be carried out in any hospital laboratory and the results should be ready within a few hours. A few drops of blood will give information on the number and appearance of all the cells in the blood. It will give a level for red blood cells (the oxygen carrying cells), platelets (small sticky squares that help to stop bruising and bleeding) and white blood cells. It will not however tell how many of the lymphocytes are B or T cells.

Test for Lymphocyte Surface Markers - (or Lymphocyte subset analysis) This is carried out if the lymphocyte count is low. It checks the numbers and ratios of the B and T cells and the subsets of T cells, especially Th (CD4), Tc (CD8) cells and NK cells. This test is less readily available but can be carried out in many larger hospitals.

Proliferative T cell response to Mitogens. This is a more specialised test, which checks that the T cells can work properly. The test stimulates the T cells to grow and multiply (proliferate). This is a useful test because as long as even a few T cells are active then the patient will usually be able to overcome immunodeficiencies associated with the 22q11.2 deletion, however it is not widely available.

Other tests are carried out to check for antibodies in the blood:
- Serum immunoglobulins - this counts the total number of antibodies in the blood and is quite easy to perform.
- Tetanus and Hib antibody titres - this checks that a child has developed protective levels of antibodies to the vaccines such as DPT and Hib and so has an immune system mature enough to respond to routine childhood vaccinations.

These tests should be repeated until the immune function has become normal.

General Advice

  • Every child with the 22q11.2 deletion will be affected differently.
  • Good hygiene can help prevent many infections, especially in the kitchen.
  • Try to avoid letting the child come into contact with people with infections, even the common cold.

Seeing a specialist:

The Children's Hospital of Philadelphia found that around 80% of children with the deletion will have some degree of immunodeficiency. They recommend that every person with the 22q11.2 deletion should have their immune system thoroughly investigated at least once by a Clinical Immunologist. Only a specialist in this area can carry out the more complex tests mentioned above and interpret the results. Your doctor can refer you.

The vast majority of those children whose immune system is affected will eventually overcome the problem but they will need varying amounts of support to fight infections during the early years. A very few will require a great deal of help, possibly even a bone marrow transplant and these children must be identified as soon as possible.

A Clinical Immunologist should see children and adults who suffer frequent infections, especially pneumonia and bronchitis. These people may benefit from treatment with immunoglobulins purified from the blood of healthy blood donors.

If your child needs surgery and a blood transfusion is likely to be needed they should be given only CMV negative and irradiated blood.

Antibiotics

Antibiotics may need to be taken regularly to prevent infection until the immune system matures. Some doctors recommend that on the discovery of a 22q11.2 deletion the broad-spectrum antibiotic co-trimoxazole (Septrin or Bactrim) should be given until the results of the investigation on immune functions are known.

If a child has a low level of T cells recurrent infections will not stimulate the immune system (, as would be the case with a normal child). Antibiotics should always be given for bacterial infections to prevent their condition from worsening.

When children lose their baby teeth or visit a dentist antibiotic cover may be required to prevent infection. This is especially important if there are heart defects that would make the child at higher risk of bacterial endocarditis. This infection can be caused by the multiple drug resistant bacteria MRSA and is very difficult to eradicate.

Growing up

Unfortunately, in some cases, the problems associated with 22q11.2 deletion during the early years can affect the social development of children who may be unable to attend nursery and other child groups. By the time these children are 5 years and start school their immune system may be functioning normally and any corrective surgery have been carried out. Missing out on vital social interaction and development stimulation is particularly important for children with the 22q11.2 deletion as there are known specific areas of learning problems also associated with the deletion.

Coping with a very sick child can have a great impact on the whole family. If children cannot be placed in a nursery one parent has to remain at home to care for the child and this may badly affect the family income. Other children may resent the attention given to the sick child.

As children grow older their ability to produce T cells improves and thus so does the rest of the immune system. The thymus is most important in the early years of life and shrinks as we get older (even healthy adults do not have a thymic shadow on X-ray).

The good news is that, as far as the immune system is concerned, the overall long term outlook for most people affected by the 22q11.2 deletion is very hopeful.