B-Cell and T-Cell Combined Disorders Workup

Updated: Aug 08, 2019
  • Author: Terry W Chin, MD, PhD; Chief Editor: Harumi Jyonouchi, MD  more...
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Laboratory Studies

Laboratory findings in the measurement of immune function are heterogeneous in patients with ataxia-telangiectasia (AT). Findings widely vary.

Decreased or absent levels of serum immunoglobulin A (IgA), immunoglobulin G (IgG)2, and immunoglobulin E (IgE) are the most common antibody abnormalities reported. In a review of 100 patients with AT, immunoglobulin deficiencies were common, affecting IgG4 in 65%, IgA in 63%, IgG2 in 48%, IgE in 23%, and IgG in 18%. All patients with AT produced IgG antibody to tetanus toxoid, whereas 76% did not respond to any of the pneumococcal polysaccharide serotypes. On the contrary, patients with AT do have increased pneumococcal antibody titers (levels lower than those of control subjects) after conjugated pneumococcal vaccination, although the vaccination may need to be repeated. [20]

Researchers recently observed hypergammaglobulinemia in 39% of 90 patients with AT. An isolated increase in immunoglobulin M (IgM) levels was the most common finding (23%). Elevated IgG levels were recorded in 2%.

The most common cellular deficiencies are absent or delayed skin-hypersensitivity reactions to tetanus and candidal antigens, depressed lymphocyte responses to mitogens, and reduced numbers of CD4+ (helper) T lymphocytes. Lymphopenia is typically present. In one study, lymphopenia affected 71% of patients with AT, with decreased B cells in 75%, CD4 T lymphocytes in 69% and CD8 T lymphocytes in 51%. The lymphocytic response to mitogens, such as phytohemagglutinin (PHA), may be in reference range or decreased. Natural killer (NK)–cell activity is in the reference range.

Despite laboratory evidence of significant immune abnormalities, opportunistic infections are uncommon. More sophisticated immune studies show normal-to-increased levels of cytokine production in both Th1 (interleukin [IL]-2, interferon [IFN]-gamma) and Th2 (IL-10, IL-4) cells. [21]

A laboratory finding unique to AT is an elevated serum alpha-fetoprotein protein (AFP) level. The karyotype reveals little or no evidence of hepatic fibrosis or hepatitis to explain the elevated AFP levels.

With the aid of molecular testing, AT can be distinguished from other autosomal recessive cerebellar ataxias, such as Friedrich ataxia, Mre11 deficiency (AT-like disease), and the oculomotor apraxias 1 (aprataxin deficiency) and 2 (senataxin deficiency). In addition, NBS1 deficiency defines Nijmegen breakage syndrome (NBS), and helicase gene defect defines Bloom syndrome.

Studies of the immune function in patients with chronic mucocutaneous candidiasis (CMC) demonstrated considerable heterogeneity, with as many as 7 groups of cellular immune responses. All patients had a defective response to candidal antigen. In some patients, defective B-cell function was also documented.

Patients with CMC do not have a delayed hypersensitivity reaction to candidal species. Patients had a normal response to other antigens, or they were anergic. In vitro tests confirmed the inability of patients' lymphocytes to proliferate or to produce certain cytokines in response to candidal antigens.

Some patients are clinically identical to other patients with CMC except that they have normal lymphocyte responses to candidal species in terms of proliferation or cytokine production. However, these same patients (with chronic localized candidiasis) do not have a delayed hypersensitivity reaction to candidal species.

Some patients have depressed levels of the IgG2 and IgG4 subclasses yet normal absolute values of IgG, IgA, and IgM. These patients appear to be unable to mount a good response to polysaccharide antigens. Hypogammaglobulinemia was reported in several other patients.

Immunoregulatory abnormalities were observed in studies of lymphocytes in vitro. Abnormal patterns of cytokine production in response to stimulation with Candida species were noted. Decreased production of some but not all type 1 cytokines (eg, IL-2 and IFN-gamma) and increased levels of IL-10 were specifically observed.

Decreased levels of NK cells were documented in 55% of 51 patients in 1 series and in 18 of 23 cases in another series. Impaired NK-cell activity against K562 target cells was seen in half of the patients described in one paper.

Whether B-cell abnormalities contribute to increased susceptibility to bacterial infections is uncertain. Deficient chemotactic activity of both neutrophils and monocytes has been described, as has abnormal antigen presentation by monocytes.

Autoantibodies against type I IFNs have been proposed as an additional diagnostic criterion for autoimmune polyglandular syndrome type I (APS I). [22]


Imaging Studies

MRI is the preferred method for radiologic evaluation in patients with AT; however, exaggerated radiographic changes are not usually visible until age 10 years. Imaging may then show ventricular dilation with diffuse cerebral atrophy. Cerebellar atrophy is marked. This finding is correlated with pathologic results showing a loss of Purkinje and granular cell layers in the cerebellum. Normal numbers of Purkinje cells at birth apparently undergo progressive degeneration.

Efforts to correlate the degree of cerebellar atrophy and the patient's ability to walk have not yielded conclusive results. This lack may be because, though the cerebellum is almost universally affected, other structures, such as anterior horn cells, dorsal columns, and peripheral nerves, may be affected to different degrees.


Other Tests

Electromyograms of patients with AT show potentials indicating disease of the anterior horn cell and correlating pathologic findings of anterior horn cell degeneration and posterior column demyelination.

Personnel in cytogenetics laboratories perform chromosomal instability tests to confirm AT and NBS to assess spontaneous and induced breakage. Chromosomal karyotyping should reveal reciprocal translocations between chromosomes 7 and 14 in AT. Absence or dysfunction of the ATM protein and mutations in the ATM gene are diagnostic findings.

Gammopathies observed in patients with AT are detected by means of immunoelectrophoresis, but they should be suspected when quantitative levels of immunoglobulin, usually IgM, are isolated.

Measurements of autoantibodies are important in patients with CMC so that the various types of CMC can be classified. Of importance, CMC can be the initial manifestation of APECED in 93% of patients. Subsequent hypoparathyroidism or adrenal insufficiency occur in these patients; mean ages of onset are 9.2 or 13.6 years, respectively.

In particularly, antibodies against interferon appear to be especially common in APS I and CMC. [23, 22]


Histologic Findings

In patients with AT, the thymus is poorly developed, with few thymocytes, absent Hassall corpuscles, and little corticomedullary demarcation.



The lifetime cancer risk for patients with AT is 10-38%. Non-Hodgkin and Hodgkin lymphomas are staged by using conventional guidelines.