Research Article Influence of Seasonality and Circulating Cytokines on Serial QuantiFERON Discordances Marsha L. Griffin, 1 Saroochi Agarwal , 1 Melissa Zhu Murphy, 2 Larry D. Teeter, 1 and Edward A. Graviss 1 1 Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA 2 Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA Correspondence should be addressed to Edward A. Graviss; eagraviss@houstonmethodist.org Received 17 October 2017; Accepted 12 February 2018; Published 12 March 2018 Academic Editor: Vincent Jarlier Copyright © 2018 Marsha L. Grifn et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. An 18-month prospective study serially tested healthcare workers (HCWs) for tuberculosis infection (TBI) and reported discordant QuantiFERON Gold In-Tube5 (QFT) results in some participants. Te purpose of the current study was to investigate whether the interferon-gamma (IFN-) measured by QFT in discordant individuals could be infuenced by other circulating cytokines that vary seasonally at the time of phlebotomy. Methods. Te CDC funded TBESC Task Order 18 (TO18) project to assess the use of Interferon Gamma Release Assays (IGRAs), T-SPOT.TB5 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 diferent time points from the Houston site was multiplexed to determine the association between circulating cytokines and antigen stimulated IFN- levels. Results. IL-12, IL-1, IL-3, GCSF, and IL-7 were associated with the amount of IFN- measured in response to antigen stimulation. In addition to these cytokines, a signifcant 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-1 and IL-3, and this upregulation was observed with the amount of IFN- measured in discordant results. 1. Introduction For over a century, the tuberculin skin test (TST) has been used to diagnose tuberculosis (TB) infection (TBI). TST detects delayed type hypersensitivity reaction to tuberculin purifed protein derivative (PPD), but the TST is only moder- ately specifc for Mycobacterium tuberculosis (Mtb) [1]. In the last decade, Interferon Gamma Release Assays (IGRAs) have been developed to improve the specifcity of TBI detection, and IGRAs directly or indirectly measure the release of interferon-gamma (IFN-) by peripheral blood mononuclear cells (PBMCs) upon stimulation by the RD1-encoded Mtb specifc antigens, ESAT-6, CFP-10, and TB7.7 (Rv2654c) [1]. During the timeframe of the present study, there were two diagnostic platforms for IGRAs: QuantiFERON-TB Gold In-Tube (QFT, Qiagen Inc., Germantown, USA) and T- SPOT.TB5 (T-SPOT, Oxford Immunotec, Marlboro, USA) approved for use in the US by the Food and Drug Admin- istration (FDA) [2]. Te QFT assay uses an enzyme-linked immunosorbent assay (ELISA) technology to indirectly mea- sure the amount of IFN- in whole blood plasma, whereas T- SPOT uses the enzyme-linked immunospot assay (ELISPOT) to measure the number of IFN- secreting T-cells in periph- eral blood mononuclear cells (PBMCs) [2]. IGRA specifcity 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]. Cytokines are immunoregulators that are important for infammation, infection, and neoplastic processes. Cytokines are circulating intercellular signaling molecules that can induce each other via cascades, and increased cytokine concentrations can lead to complex systemic efects such as fever, shock, and chronic infammation. Chemokines, a Hindawi Tuberculosis Research and Treatment Volume 2018, Article ID 6731207, 5 pages https://doi.org/10.1155/2018/6731207