Influence of Seasonality and Circulating Cytokines on Serial QuantiFERON Discordances.

Marsha L Griffin,Saroochi Agarwal,Edward A Graviss,Larry D Teeter,Melissa Zhu Murphy

doi:10.1155/2018/6731207

Abstract

Objectives. An 18-month prospective study serially tested healthcare workers (HCWs) for tuberculosis infection (TBI) and reported discordant QuantiFERON Gold In-Tube® (QFT) results in some participants. The purpose of the current study was to investigate whether the interferon-gamma (IFN-γ) measured by QFT in discordant individuals could be influenced by other circulating cytokines that vary seasonally at the time of phlebotomy. Methods. The CDC funded TBESC Task Order 18 (TO18) project to assess the use of Interferon Gamma Release Assays (IGRAs), T-SPOT.TB® and QFT, compared to the tuberculin skin test (TST) for the serial testing of TBI in HCW at 4 US sites. Unstimulated plasma from 9 discordant TO18 participants at 4 different time points from the Houston site was multiplexed to determine the association between circulating cytokines and antigen stimulated IFN-γ levels. Results. IL-12, IL-1β, IL-3, GCSF, and IL-7 were associated with the amount of IFN-γ measured in response to antigen stimulation. In addition to these cytokines, a significant relationship was found between a positive QFT result and the spring season. Conclusions. Allergens during the spring season can result in the upregulation of IL-1β and IL-3, and this upregulation was observed with the amount of IFN-γ measured in discordant results.

Highlights

For over a century, the tuberculin skin test (TST) has been used to diagnose tuberculosis (TB) infection (TBI)
Among all the cofactors in the Generalized Estimating Equation (GEE) modeling technique showing significance, spring season, identified as 3 months (March–May) of the year when phlebotomization occurred, had a coefficient of 33.097 that corresponds to an increase of 33 pg of IFN-γ produced (Table 1), and spring seasonality accounted for 64% of all QuantiFERON Gold In-Tube5 (QFT) positive results (Table 2)
The measured IFN-γ production upon stimulation by Mycobacterium tuberculosis (Mtb) antigens was often highest at the spring season time point among the serially tested healthcare workers (HCWs) with discordant results (Figure 1)

Summary

Introduction

The tuberculin skin test (TST) has been used to diagnose tuberculosis (TB) infection (TBI). TST detects delayed type hypersensitivity reaction to tuberculin purified protein derivative (PPD), but the TST is only moderately specific for Mycobacterium tuberculosis (Mtb) [1]. Interferon Gamma Release Assays (IGRAs) have been developed to improve the specificity of TBI detection, and IGRAs directly or indirectly measure the release of interferon-gamma (IFN-γ) by peripheral blood mononuclear cells (PBMCs) upon stimulation by the RD1-encoded Mtb specific antigens, ESAT-6, CFP-10, and TB7.7 (Rv2654c) [1]. The QFT assay uses an enzyme-linked immunosorbent assay (ELISA) technology to indirectly measure the amount of IFN-γ in whole blood plasma, whereas TSPOT uses the enzyme-linked immunospot assay (ELISPOT) to measure the number of IFN-γ secreting T-cells in peripheral blood mononuclear cells (PBMCs) [2]. IGRA specificity for the diagnosis of TBI using the QFT and T-SPOT has been estimated to be 65.8% and 74.5%, respectively, and the sensitivities of QFT and T-SPOT are 84.0 and 84.2%, respectively [3]

Objectives

Methods

Results

Conclusion