Predictive value of TNF-\u03b1, IFN-\u03b3, and IL-10 for tuberculosis among recently exposed contacts in the United States and Canada

Mary R Reichler,Neil W Schluger ,Susan E Dorman,Yan Yuan,Christina S Hirsch ,Abdul Qadir Khan ,Timothy R Sterling

doi:10.1186/s12879-020-05185-2

Abstract

BackgroundWe examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis.MethodsWe prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays.ResultsOf 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P < .01; IFN-γ 231 versus 27, P < .001), and those who subsequently developed incident tuberculosis had higher median baseline TNF-α concentrations (in pg/mL, 257 vs. 71, P < .05). In multivariate analysis, contact age < 15 years, US/Canadian birth, and IFN or TNF concentrations > the median were associated with co-prevalent tuberculosis (P < .01 for each); female sex (P = .03) and smoking (P < .01) were associated with incident tuberculosis. In algorithms combining young age, positive skin test results, and elevated CFPS TNF-α, IFN-γ, and IL-10 responses, the positive predictive values for co-prevalent and incident tuberculosis were 40 and 25%, respectively.ConclusionsCytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis.

Highlights

We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis
Tumor necrosis factor alpha (TNF-α) response to M. tuberculosis antigens may be elevated and IFN-γ response depressed at the time of TB diagnosis, with a later decline in TNF-α and elevation of IFN-γ associated with successful resolution of disease [3,4,5]
These findings indicate that CFPS TNF-α and IFN-γ responses might be useful tools for predicting active TB and prompt consideration of their use during contact investigation

Summary

Introduction

We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis. A better understanding of the immunologic and epidemiologic profiles associated with Mycobacterium tuberculosis infection and disease after TB exposure can help focus TB control efforts. Identification of surrogate markers of protective immunity against M. tuberculosis infection and TB disease can aid development of new TB vaccines. Immune responses among persons with TB disease have been the subject of multiple studies. An increase in TNF-α has been observed among persons with previously treated TB disease at the time of relapse [5]. IL-10 is known to be elevated early in the course of TB disease, and is believed to function as an inhibitor to regulate and help prevent the potentially destructive effects of an over vigorous immune response [7]

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