Immunodeficiency and infections in ataxia-telangiectasia

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Abstract

Objective

To characterize the immunodeficiency in ataxia-telangiectasia (A-T) and to determine whether the immunodeficiency is progressive and associated with increased susceptibility to infections.

Study design

Records of 100 consecutive patients with A-T from the Johns Hopkins Ataxia-Telangiectasia Clinical Center (ATCC) were reviewed.

Results

Immunoglobulin (Ig) deficiencies are common, affecting IgG4 in 65% of patients, IgA in 63%, IgG2 in 48%, IgE in 23%, and IgG in 18%. Lymphopenia affected 71% of patients, with reduced B-lymphocyte number in 75%, CD4 T lymphocytes in 69%, and CD8 T lymphocytes in 51%. There was no trend for increased frequency or severity of immune abnormalities with age. Recurrent upper and lower respiratory tract infections were frequent: otitis media in 46% of patients, sinusitis in 27%, bronchitis in 19%, and pneumonia in 15%. Sepsis occurred in 5 patients, in 2 patients concurrent with cancer chemotherapy. Warts affected 17% of patients, herpes simplex 8%, molluscum contagiosum 5%, candidal esophagitis 3%, and herpes zoster 2%. Uncomplicated varicella infection occurred in 44% of patients; 2 patients had more than one clinical episode. No patient had Pneumocystis jerovici pneumonia or a complication of live viral vaccine.

Conclusions

In spite of the high prevalence of laboratory immunologic abnormalities, systemic bacterial, severe viral, and opportunistic infections are uncommon in A-T. Cross-sectional analysis suggests that the immune defect is rarely progressive.

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

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    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.

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