Abstract

Interferon-Gamma Release Assays (IGRAs) in the past decade have become ubiquitous screening for tuberculosis (TB). Development of these interferon release tests helped screen for TB in patients at high risk, specifically those with human immunodeficiency virus (HIV). The blood test was designed to strongly stimulate interferon release when blood was exposed to a tube laced with TB antigens. Cut points were established so that any interferon measurement over 35 IU is considered a "positive" test for TB. Sero-positive rheumatoid patients (RA) spontaneously produce interferon. During an IGRA test in a sero-positive RA patient, the interferon levels are often over 35 IU, but without exposure to TB. We found the interferon test results from 16 sero-positive RA patients correlated with the level of cyclic citrullinated protein (p < 0.02). After treatment of RA, the IGRA test Interferon-Gold, alternated between positive and negative. This test designed originally for HIV patients, is not ideal for sero-positive RA patients where interferon is produced spontaneously. This report describes a small series of 16 sero-positive RA patients without TB in the United States, all with false positive Interferon-Gold testing. The interferon test is a screening test only, and not a diagnostic test. As with many diagnoses in medicine, tests should be evaluated in context. In one illustrative case, the Interferon-Gold test was misleading, incorrect treatment administered, and the RA patient died. TB may be falsely accused. TB is not diagnosed by an interferon level in RA, and should be diagnosed by culture, m-RNA, or acid-fast positive smear. In RA, the better TB screening test is the skin purified protein derivative (PPD) which tests type 4 delayed hypersensitivity and not interferon levels. Data has shown with use of biologic and immune modulating therapies, that the leading life-threatening infections are bacterial pneumonias. False positive TB interferon tests are not helpful.

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