Immunologic Abnormalities and Infections in Patients with Ataxia-Telangiectasia

Dr Howard M Lederman

The following is a summary of Dr Lederman's talk for the A-T Study/Awareness Day on 20 November 1997 at Nottingham City Hospital's Post-Graduate Education Centre, organised by The A-T Appeal

Immunologic abnormalities are common among patients with A-T. There is a progressive T-lymphocytopenia with anergy (lack of delayed-type hypersensitivity skin tests responses) in as many as 25% of patients. However, clinically important cellular immunodeficiency is quite rare except for the presence of chronic/disseminated warts in a minority of patients. Abnormalities of humoral immunity are common and also progressive. Approximately 50% of A-T patients will develop IgA deficiency. A smaller number will have deficiencies of one or more IgG subclasses, or problems producing antibody in response to vaccines. We have recently identified monoclonal or oligoclonal gammopathies in almost 10% of A-T patients. The significance of this finding is not known, but several of the patients have developed arthritis, splenomegely and hyperviscosity.

The most frequent and serious infections in A-T patients involve the lungs (bronchitis and pneumonia). In some individuals, underlying immunodeficiency plays an important role in susceptibility to infection. In other cases, the susceptibility to lung infection results from dysfunctional swallow, ineffective cough reflex, and aspiration.

We have the following recommendations:

  1. Immunologic evaluation for patients who appear to have an increased susceptibility to infection (increased number or more severe infections). This evaluation should include:

    • measurement of serum immunoglobulin levels (IgG, IgA, IgM)
    • immunofixation electrophoresis to detect gammopathy
    • measurement of antibody responses to protein (diphtheria, tetanus) and polysaccharide (pneumococcal) vaccines

  2. Consider antibiotic prophylaxia and/or immunoglobulin replacement for patients with deficiency of antibody responses.

  3. If humoral immunity is normal

    • administer all standard childhood vaccines, including measles/mumps/rubella and varicella vaccines.
    • administer pneumococal vaccine at age 2 years with booster doses every 5-7 years
    • administer influenza virus vaccine every year for patient and all household members.

  4. All A-T patients with frequent pulmonary infections should have a feeling/swallowing evaluation to identify those patients with aspiration.

  5. Prophylaxis for Pneumocystis carinii is probably unnecessary even in patients with severe lymphopenia, unless there is a history of other opportunistic infections.

Dr Howard M Lederman MD
Consultant Immunologist &
Director of the A-T Clinical Center
Johns Hopkins Hospital
Baltimore, MD

OTHER PRESENTATIONS:

Ataxia Telangiectasia: 1926 - 1997 - An Introduction

Professor Sarah Bundey, Department of Clinical Genetics, Birmingham Women's Hospital

Increased Radiation Sensitivity and Cancer Associated with Ataxia-Telangiectasia

Professor Malcolm Taylor, CRC Laboratories, Department of Cancer Studies, University of Birmingham

The Neurological Aspects of Ataxia-Telangiectasia

Dr Graham Lennox, Consultant Neurologist, Queen's Medical Centre, University Hospital, Nottingham

Ataxia-Telangiectasia and ATM: The Next Stage

Professor Yosef Shiloh, Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Israel

Why it is Important to Identify Cases of Ataxia-Telangiectasia

Professor Sandy Raeburn, Centre for Medical Genetics, University of Nottingham

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