Immunodeficiency and infections in ataxia-telangiectasia☆
Section snippets
Methods
The charts of the first 100 consecutive patients with confirmed A-T evaluated at the Johns Hopkins ATCC were reviewed. The patients were referred by their physicians or were self-referred for a multidisciplinary assessment. Patients were considered to have A-T if they displayed characteristic neurologic features (ataxia, oculomotor abnormalities, and dysarthria) and at least one of the following laboratory abnormalities: elevated serum alpha-fetoprotein (AFP) level, increased x-ray-induced
Antibody levels
The most common humoral immune abnormality (defined as a value more than 2 standard deviations above or below the mean for age) was serum IgG4 deficiency (65%), followed by IgA deficiency (63%), IgG2 deficiency (48%), IgE deficiency (23%), and IgG deficiency (18%), as documented by the first immunologic evaluation for each patient (Table I). Among patients with IgA deficiency, 24% had isolated IgA deficiency, 32% had IgG4 deficiency, 11% had IgG2 deficiency, 24% had both IgG2 and IgG4
Discussion
There is a wide range of immunologic abnormalities in A-T that affects both humoral and cell-mediated immunity. Humoral immunodeficiency in our cohort is similar to that described in smaller collections of A-T patients. The most common abnormalities are the absence or marked reduction of IgA,10., 11. IgG subclasses—in particular, IgG4 and IgG26., 10., 19.—and IgE.5., 20. Antibody responses to vaccines are normal in some A-T patients but reduced in others.7., 10. The pathophysiologic basis for
References (36)
Ataxia telangiectasia
Semin Pediatr Neurol
(1998)- et al.
Lymphoid tissue abnormalities associated with ataxia-telangiectasia
Am J Med
(1966) Early diagnosis of ataxia-telangiectasia using radiosensitivity testing
J Pediatr
(2002)- et al.
Immunoglobulins in ataxia-telangiectasia: evidence for IgG4 and IgA2 subclass deficiencies
Clin Immunol Immunopathol
(1981) Oropharyngeal dysphagia and aspiration in patients with ataxia-telangiectasia
J Pediatr
(2000)- et al.
Ataxia-telangiectasia in a child with vaccine-associated paralytic poliomyelitis
J Pediatr
(1992) A single ataxia telangiectasia gene with a product similar to PI-3 kinase
Science
(1995)- et al.
The genetic defect in ataxia-telangiectasia
Annu Rev Immunol
(1997) - et al.
The many substrates and functions of ATM
Nat Rev Mol Cell Biol
(2000) - et al.
Immunoglobulin E deficiency in ataxia-telangiectasia
N Engl J Med
(1969)
IgG2 deficiency in ataxia-telangiectasia
N Engl J Med
Heterogeneity of the immunological deficiency in ataxia-telangiectasia: absence of a clinical-pathological correlation
Kroc Found Ser
Twenty-year follow-up of 160 patients with ataxia-telangiectasia
Turk J Pediatr
Oligo-/monoclonal gammopathy and hypergammaglobulinemia in ataxia-telangiectasia: a study of 90 patients
Medicine (Baltimore)
Impaired IgG antibody production to pneumococcal polysaccharides in patients with ataxia-telangiectasia
J Clin Immunol
Immunological abnormalities in ataxia telangiectasia
Heterogeneity of immunological abnormalities in ataxia-telangiectasia
J Clin Immunol
Impaired autologous mixed lymphocyte reaction (AMLR) in patients with ataxia-telangiectasia and their family members
Clin Exp Immunol
Cited by (259)
Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review
2024, Genetics in MedicineCausative mechanisms and clinical impact of immunoglobulin deficiencies in ataxia telangiectasia
2024, Journal of Allergy and Clinical ImmunologySomatic and germline ATM variants in non-small-cell lung cancer: Therapeutic implications
2023, Critical Reviews in Oncology/HematologyGenome integrity and inflammation in the nervous system
2022, DNA RepairInfections in primary immunodeficiency
2022, Allergic and Immunologic Diseases: A Practical Guide to the Evaluation, Diagnosis and Management of Allergic and Immunologic Diseases
- ☆
Supported by Ataxia-Telangiectasia Children's Project, Deerfield Beach, FL; and Pediatric Clinical Research Center, The Johns Hopkins Hospital, Baltimore, MD, Grant RR00052, Division of Research Resources, National Institutes of Health.