Immunodeficiency and Predisposition to Infection

About two-thirds of people with A-T have abnormalities of the immune system detected by the laboratory, but not all of them cause symptoms. The most common laboratory abnormalities are:

• Low levels of one or more classes of immunoglobulin (IgG, IgA, IgM, or IgG subclasses)
• Impaired antibody responses to vaccines or infections
• Low numbers of lymphocytes (especially T-lymphocytes) in the blood

Immunodeficiency is one of the factors that can predispose people with A-T to develop frequent infections of the upper (colds, sinusitis, and ear infections) and lower (bronchitis and pneumonia) respiratory tract.

Managing Immunodeficiency and Predisposition to Infections

All individuals with A-T should have at least one comprehensive immunologic evaluation that measures:

• Levels of serum immunoglobulins (IgG, IgA, and IgM)
• Antibody responses to T-dependent (e.g., Pneumococcal conjugate such as Prevnar, Hemophilus influenzae b, tetanus) and T-independent (23-valent pneumococcal polysaccharide) vaccines
• Number and type of lymphocytes in the blood (CD4 and CD8 T-lymphocytes and B-lymphocytes)

If results show significant abnormalities of the immune system, an allergist, immunologist or infectious disease specialist will be able to discuss various treatment options, which might include the use of gamma globulin, prophylactic antibiotics and minimized exposure to infection.

Sometimes vaccines can overcome other problems causing a predisposition to infection. Vaccines against common bacterial respiratory pathogens such as Hemophilus influenzae, pneumococci, and influenza virus (the “flu”) are commercially available and often help to boost antibody responses, even in individuals with low immunoglobulin levels. (See Vaccine Schedules below.) If vaccines do not work and the person with A-T continues to have problems with infections, gamma globulin therapy (IV or subcutaneous infusions of antibodies collected from normal individuals) may help.

Typically, the pattern of immunodeficiency seen in a person with A-T by age five will be the same pattern seen throughout that person’s life. However, 10-20% of people with A-T will have immunologic function deteriorate as they get older. It is thus worthwhile to reassess immune function if problems with infections become more severe at any age.

Additionally, if infections are in the lungs, assessing the person’s swallowing is important as swallowing incoordination may cause aspiration into the lungs leading to infections. (See Feeding, Swallowing, and Nutrition.)

Most people with A-T have low lymphocyte counts in the blood, often specifically affecting a certain kind of lymphocyte called the CD4 T-cell. This seldom causes problems except for a tendency to have chronic or recurrent viral infections of the skin such as warts and molluscum contagiosum. Treatment for low CD4 cell number is seldom required but should be considered if a person with A-T is treated with corticosteroid drugs such as prednisone for longer than a few weeks or is treated with chemotherapy for cancer. Under those circumstances, antibiotics may be recommended to prevent infections caused by a specific group of germs (opportunistic pathogens).

People with A-T  have an increased risk of developing autoimmune or chronic inflammatory diseases. This risk is probably a secondary effect of their immunodeficiency and not a direct effect of the lack of ATM protein. The most common examples of such disorders in A-T include immune thrombocytopenia (ITP), arthritis, and vitiligo.

Vaccine Schedules

• If antibody function is normal, all routine childhood immunizations including live viral vaccines should be given, except the measles/mumps/rubella (MMR) vaccine. (That vaccine may be related to the development of chronic skin sores called granulomas in a very small number of people with A-T.) We recommend special attention to vaccines that can prevent influenza (the “flu”) and some forms of pneumonia.
• People with A-T and all household members should receive the killed (injected) influenza vaccine every fall.
• People with A-T older than two years who have not previously been immunized with Prevnar should receive two (2) doses of Prevnar. At least six months after the last Prevnar has been given and after the child is at least two years old, a 23-valent pneumococcal vaccine (Pneumovax) should be administered. Immunization with the Prevnar vaccine should be repeated approximately every five years for children and adults.