Beyond QuantiFERON-TB Results, the Added Value of a Weak Mitogen Response

Abstract

Introduction: While QuantiFERON-TB gold (QFT) is frequently used, little attention is paid to the mitogen response. How it could be impacted and associated with outcomes is poorly known.

Methods: Retrospective, case-control study in hospitalized patients who underwent QFT testing in two hospitals between 2016 and 2019. We defined two groups of cases with either negative [interferon (IFN)-γ ≤ 0.5 IU/ml, official threshold] or weak (0.5-2 IU/ml) mitogen response, and one group of controls with normal (>2 IU/ml) mitogen response.

Results: A total of 872 patients were included. An ongoing infection was independently associated with both a negative (RR = 4.34; 95% CI = 2.94-6.41) and a weak mitogen response (RR = 2.44; 95% CI = 1.66-3.58). Among tuberculosis patients, a weak mitogen response was associated with a false-negative QFT result (75%) compared to a normal response (20%). Decreasing mitogen response (normal, weak and negative, respectively) was associated with increasing length of hospital stay [median (interquartile range) 5 (3-13), 11 (5-21) and 15 (10-30) days; p < 0.001] and increasing hospital mortality (3, 7, and 15%; p < 0.001).

Conclusion: Clinicians should take notice of the mitogen response since IFN-γ concentrations lower than <2 IU/ml were associated with false-negative QFT results in tuberculosis patients, independently associated with ongoing infections, and could be associated with worse prognosis.

Keywords: QuantiFERON; infection; mitogen; mortality; outcomes.

FIGURE 1

Inverse correlation between INF-γ mitogen response and C-reactive protein levels in hospitalized patients. Correlation between INF-γ mitogen response of QFT and C-reactive protein levels was assessed in hospitalized patients included in the study and with available C-reactive protein data (n = 825); Spearman test. NB: IFN-γ, interferon γ, QFT, QuantiFERON-TB Gold.

FIGURE 2

Clinical outcomes of 872 hospitalized patients according to the mitogen response of QFT (negative, weak or normal). Proportion of patients with infectious complications during hospital stay after QFT sampling (A), intensive care unit (ICU) admissions (B), in-hospital mortality (C) and the median (interquartile range) hospital length of stay (D) were recorded and represented according to the mitogen response: negative (IFN-γ ≤ 0.5 IU/ml), weak (IFN-γ = 0.5–2 IU/ml) and “normal” (IFN-γ > 2 IU/ml). NB: QFT, QuantiFERON-TB Gold; ICU, intensive care unit; IFN-γ, interferon γ. Comparisons were made between the 3 groups using Kruskall-Wallis test for continuous variable, and the Chi-square test for qualitative variables. Post-hoc 2 × 2 comparisons were performed using the Wilcoxon Mann-Whitney test and Chi-square test as appropriate. False Discovery Rate post hoc correction for multiple comparisons was used and P value reported in the figure : *P < 0.05; **P < 0.01.