What is the role of lab testing in the diagnosis of common variable immunodeficiency (CVID)?

Updated: Feb 23, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
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Answer

An assessment of functional antibody production in response to natural antigens or antigens to which the population is commonly exposed may be helpful. Similarly, an evaluation of the antibody response after active immunization with polysaccharide or protein antigens is possible.

However, because the nonresponse rate to hepatitis B is so high, especially among persons older than 40 years, these antigens remain unreliable in the testing of immune competence.

Circulating T and B lymphocytes can be assessed by using monoclonal antibodies for immunofluorescence staining. CD19 and CD20 (B cells), CD3 (T cells), CD4 (helper T cells), and CD8 (suppressor T cells) are all commonly used.

Natural killer (NK) cells also express CD3 and CD8 surface proteins. Therefore, NK cells and T cells can be further enumerated by using monoclonal antibodies against CD16, CD56, and CD57, though they are not lineage specific.

The in vivo measurement of T-cell function is possible by using an anergy panel to assess localized immunologic skin responses.

The antigens most commonly used include mumps (1 mg/mL), although availability of this antigen has varied; trichophytin (1:30 dilution); purified protein derivative (PPD) (2-10 IU); Candida antigen (1:100 dilution); and tetanus fluid toxoid (1:1000 dilution). An intradermal injection of 0.1 mL of antigen is necessary to perform the test.

The results should be read 48-72 hours after the injection to ensure an induration of maximal diameter. A positive test result indicates intact delayed-type hypersensitivity. A negative test result to all antigens suggests impaired type IV immunity. Erythema around the injection site does not indicate a positive result.

To assess the functional activity of the lymphocytes in vitro, they must be isolated and stimulated with a variety of agents. One class of activators is the mitogens, which includes phytohemagglutinin and concanavalin A, both of which stimulate T cells. Pokeweed mitogen promotes proliferation of both T and B lymphocytes.

Another class of stimulators includes antigens. PPD, streptokinase, Candida antigen, and tetanus toxoid all activate lymphocytes, if the patient has had a prior exposure to the antigen or superantigen.

Allogeneic cells can also act as activators. They stimulate T-cell proliferation in mixed lymphocyte cultures. The proliferation of lymphocytes can be activated by in vitro antibodies to T-cell surface molecules that are important in signal transduction. These molecules include CD3, CD2, CD28, and CD43.

T-cell activity can be directly studied. T lymphocytes express certain antigens after activation. These antigens include CD69, IL-2 receptor (CD25), transferring receptors (CD71), and major histocompatibility complex class II molecules (human leukocyte antigen DR).

Measuring the levels of mediators and cytokines such as IL-2, IL-4, IL-5, interleukin 6 (IL-6), interferon gamma, and tumor necrosis factor in the culture supernatant is another useful tool.

Another method is the measurement of levels of secreted Ig in the culture supernatant. The complete blood count and autoantibody testing may be helpful as well. Anemia secondary to an autoimmune process may be detected. Severe lymphopenia may indicate that the patient has severe combined immunodeficiency disease or other primary T-cell defects.


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