A 26-year-old man with a history of Crohn disease is being evaluated for initiation of anti-tumor necrosis factor therapy. The patient has had progressively severe ileocolitis despite taking glucocorticoids for several weeks. Interferon-gamma release assay is performed. During the test, the interferon-gamma level in the patient's blood sample is measured at baseline and after incubating the sample with control antigens and mycobacterial antigens. The results are as follows: HIV testing is negative. Which of the following best explains the results of this patient's interferon-gamma release assay?

Question

A 26-year-old man with a history of Crohn disease is being evaluated for initiation of anti-tumor necrosis factor therapy.  The patient has had progressively severe ileocolitis despite taking glucocorticoids for several weeks.  Interferon-gamma release assay is performed.  During the test, the interferon-gamma level in the patient's blood sample is measured at baseline and after incubating the sample with control antigens and mycobacterial antigens.  The results are as follows: HIV testing is negative.  Which of the following best explains the results of this patient's interferon-gamma release assay?

Quizplus · Accepted Answer

Exposure of this patient's blood to a control agent does not significantly stimulate interferon-gamma release above baseline, indicating a lack of lymphocyte response to a strong stimulatory mitogen. This is considered an indeterminate result because lymphocytes are unable to release significant quantities of interferon-gamma whether or not they have been previously exposed to Mycobacterium tuberculosis antigens. A minimal response to control antigens is most often seen with lymphocyte immunosuppression due to HIV or the use of immunomodulatory medications (eg, glucocorticoids). In patients with HIV, testing should be repeated when CD4 counts improve with antiretroviral therapy; in those taking immunomodulatory medications, testing should be repeated after these medications have been discontinued for a couple of weeks. This usually restores the ability of lymphocytes to generate interferon-gamma to a control mitogen, thereby allowing interpretation of interferon-gamma release in response to M tuberculosis antigens. Evaluation for latent tuberculosis infection with either the interferon-gamma release assay (IGRA) or tuberculin skin test (TST) should be performed prior to the initiation of anti-tumor necrosis factor therapy (which increases the risk of reactivation tuberculosis). Because IGRA uses antigens fairly specific for tuberculous mycobacteria, it is more sensitive and specific than TST. Furthermore, because IGRA identifies antigens that are not present in Mycobacterium bovis, test results are not typically affected by previous vaccination with bacille Calmette-Guérin (a live strain of M bovis sometimes used as a vaccine against tuberculosis) (Choice B). (Choices A and D) Active and latent tuberculosis are both marked by elevated levels of interferon-gamma in response to mycobacterial antigens (positive IGRA); definitive diagnosis of active TB also requires microbial diagnosis (identification of the organism in culture). In this case, however, the lack of response to control antigens makes the IGRA results to mycobacterial antigens impossible to interpret. (Choice C) Indeterminate IGRA results can also be seen with concurrent inflammation or ongoing non-TB infections that provoke interferon-gamma release. However, in such situations, patients would have high baseline levels of interferon-gamma (unlike in this patient). Educational objective: Interferon-gamma release assay measures lymphocyte response to tuberculous antigens. An indeterminate result can occur when patients have high background interferon-gamma levels due to ongoing inflammation or concurrent infection; it can also occur when there is minimal response to control mitogens due to lymphocyte suppression from HIV or immunomodulatory medications (eg, glucocorticoids).

A 26-Year-Old Man with a History of Crohn Disease Is