Defective Antigen Tubes Generate False-Positive QuantiFERON Tuberculosis Test Results

TO THE EDITOR—In recent years a significant shift in testing has occurred for diagnosing latent tuberculosis (LTB). The adoption of interferon gamma release assays (IGRA) has largely supplanted tuberculin skin test (TST) for both patient testing and employee screening. IGRA have advantages over TST in that they are unaffected by prior vaccination with bacillus Calmette–Guérin (BCG) vaccine and do not require a patient or employee return to clinic to have the test interpreted. There have been significant concerns over perceived false-positivity rates when using these assays in low risk populations such as employee screening due to suboptimal interpretive cutoffs as well as defective collection tubes [1, 2]. A recent 2012 tube recall initiated by the manufacturer did not result in a noticeable increase in our positivity since our large test volumes typically encompass multiple concurrent tube lots, and therefore we rely on individual hospitals to communicate suspicious trends to our lab for thorough investigation. We recently encountered a suspected quality issue for QuantiFERON (QTF) TB antigen tubes of significant concern to the medical community. University of Wisconsin Medical Foundation Laboratories (UWMF) contacted our laboratory in response to multiple suspected falsepositive results from laboratory staff members. The individuals had no risk factors for LTB. The tubes responsible for these spurious results belonged to antigen lot A130400Z. Previous lots had not resulted in false-positives for UWMF. We performed a dual site, co-collection from healthy volunteers on 12 tube sets from A130400Z and a lot with acceptable positivity rates. In sum, 4 paired sets were drawn at UWMF, and 8 sets were drawn at ARUP. Two discrepant test results were generated at each site (4/12 or 33%), in which the volunteer was positive on lot A130400Z and negative on the other (Table 1). Based on these data, we unilaterally and proactively recalled all remaining A130400Z tubes from our submitting institutions, though the manufacturer did not deem these data sufficient to warrant a company-initiated recall. We then co-collected 65 healthy volunteers at our laboratory who met specific inclusion criteria. Seventeen of the 65 test results were discrepant with positive results on the A130400Z tube only (Table 1). Combined with the first data set, this equates to a 27.3% false-positivity rate for A130400Z. Based on these data and a recent realtime positivity analysis related to suspected defective tubes, physicians must use extreme care when interpreting results from IGRAs [3]. Of note, A130400Z was not previously identified as being defective [3]. Though these false-positives may prove to be inconvenient for employee screening purposes and institutional cost containment, the larger concern is clinical harm due to patient testing using these defective tubes. Though QTF positive results are often repeated Table 1. Discrepant Quantiferon Testing Results From Co-collection of Volunteer Blood Donors That Met Defined Inclusion Criteria