Close contact interferon-gamma response to the new PstS1(285\u2013374):CPF10: a preliminary 1-year follow-up study

Leonardo Silva De Araujo,Nidai ,Fernanda Carvalho Queiroz Mello,Janaina Aparecida Medeiros Leung,Maria Helena Féres Saad

doi:10.1186/s13104-016-2360-4

Abstract

BackgroundThe available diagnostic tools for latent tuberculosis (TB) infection (LTBI) via interferon-gamma (IFN-g) release assays (IGRA) are based on ESAT6:CFP10 stimulation. However, the mycobacterial antigen PstS1 is also highly immunogenic and some of its fragments, such as PstS1(285–374), have shown higher immunoreactivity in LTBI than in active TB. PstS1(285–374), therefore, could increase the accuracy of the existing IGRA to detect LTBI. Thus, a new chimeric protein has recently been developed (PstS1(285–374):CFP10) showing potential for LTBI screening of recent close contacts (rCt) exposed to Mycobacterium tuberculosis. The aim of this study was to analyze the PstS1(285–374):CFP10 longitudinal IFN-g profile in comparison to ESAT6:CFP10 and full PstS1/CFP10 stimulation in a rCt cohort and correlate the responses to these in-house IGRA with any clinical changes/interventions that might occur.MethodsA free-of-cost, one-year follow up was offered to 120 rCt recruited in Rio de Janeiro, RJ, Brazil. Whole blood short-term (WBA), long-term stimulation (LSA) assays, and the tuberculin skin test (TST) were performed during follow up.ResultsAmong the enrolled rCt, 44.2% (53/120) returned for re-evaluation and the control group (TST negative, n = 17) showed low IFN-g reactivity to all antigen stimulations during the entire follow up, except for one participant who had shown radiological evidence of past TB/LTBI. Both incident cases were detected by IGRA-PstS1(285–374):CFP10 during LTBI and after disease progression. Moreover, subsequent to the prophylactic treatment for LTBI (tLTBI), a significant regression in the LSA response was predominantly observed through stimulation of the new chimeric protein (8/10, 80%) followed by ESAT6:CFP10 (5/10, 50%) and PstS1/CFP10 (4/10, 40%). No clinical or epidemiological characteristics were exclusively shared among IGRA convertors.ConclusionIt was demonstrated that the TST negative rCt without radiological evidence of LTBI/TB did not develop an IGRA-PstS1(285–374):CFP10 response during the one-year follow up. Moreover, all incident cases were detected by our new IGRA; and a significant decrement of LSA-PstS1(285–374):CFP10 reactivity post-prophylactic tLTBI was found. To our knowledge, this is the first study to monitor changes in the immune response profile of IGRA-PstS1(285–374):CFP10 among rCt during a consecutive one-year period, thus providing additional evidence of its potential in the detection of LTBI.

Highlights

The available diagnostic tools for latent tuberculosis (TB) infection (LTBI) via interferon-gamma (IFN-g) release assays (IGRA) are based on ESAT6:CFP10 stimulation
Of all enrolled recent close contacts (rCt), 44.2% (53/120) returned for the 1-year reevaluation. They were organized into study groups according to their baseline TST and clinical outcomes, as follows: Group I, TST negative (TSTneg: Whole blood short-term assay (WBA), n = 10; long-term stimulation (LSA), n = 17); Group II, TST conversion (WBA, n = 2; LSA, n = 4); Group III, TST positive (TSTpos) submitted to treatment for LTBI (tLTBI) (WBA, n = 17; LSA, n = 25); Group IV, TSTpos untreated (WBA, n = 4; LSA, n = 5); and Group V: TB incident cases (WBA, n = 2; LSA, n = 2) (Fig. 1)
The sample size and prophylactic tLTBI are limitations, which may contribute to an underestimation of the negative/positive predictive values of the test to detect TB progression

Summary

Introduction

The available diagnostic tools for latent tuberculosis (TB) infection (LTBI) via interferon-gamma (IFN-g) release assays (IGRA) are based on ESAT6:CFP10 stimulation. Notwithstanding the evidence afforded by longitudinal studies suggesting that, among high-risk populations, TST is more sensitive [10] and cost-effective [2], there is a global tendency, especially in high-income countries, to replace TST by a single-step commercial IGRA-RD1 or apply it after a prior TST screening [11]. These approaches would necessarily increase the financial burden of global TB control programs, primarily in lowand middle-income countries [1, 12]. The need for new, more cost-effective, and reliable tools/antigens that could safely substitute or add sensitivity to the LTBI biomarkers currently in use continues to exist

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