DOI: 10.5061/dryad.g91p3
title: Data from: Establishment of elevated serum levels of IL-10, IL-8 and TNF-beta as potential peripheral blood biomarkers in tubercular lymphadenitis: a prospective observational cohort study

description: Background: Tubercular lymphadenitis (TL) is the most common form of
 extra-pulmonary tuberculosis (TB) consisting about 15-20% of all TB cases.
 The currently available diagnostic modalities for (TL), are invasive and
 involve a high index of suspicion, having limited accuracy. We
 hypothesized that TL would have a distinct cytokine signature that would
 distinguish it from pulmonary TB (PTB), peripheral tubercular
 lymphadenopathy (LNTB), healthy controls (HC), other lymphadenopathies
 (LAP) and cancerous LAP. To assess this twelve cytokines (Tumor Necrosis
 Factor (TNF) -alpha, Interferon (IFN) -gamma, Interleukin (IL)-2, IL-12,
 IL-18, IL-1beta, IL-10, IL-6, IL-4, IL-1 Receptor antagonist (IL-1Ra),
 IL-8 and TNF-beta, which have a role in pathogenesis of tuberculosis, were
 tested as potential peripheral blood biomarkers to aid the diagnosis of TL
 when routine investigations prove to be of limited value. Methods and
 Findings: A prospective observational cohort study carried out during
 2010-2013. This was a multi-center study with three participating
 hospitals in Delhi, India where through random sampling cohorts were
 established. The subjects were above 15 years of age, HIV-negative with no
 predisposing ailments to TB (n = 338). The discovery cohort (n= 218) had
 LNTB (n = 50), PTB (n = 84) and HC (n = 84). The independent validation
 cohort (n=120) composed of patients with cancerous LAP (n=35), other LAP
 (n=20) as well as with independent PTB (n=30), LNTB (n=15) and HC (n=20).
 Eight out of twelve cytokines achieved statistical relevance upon
 evaluation by pairwise and ROC analysis. Further, variable selection using
 random forest backward elimination revealed six serum biosignatures
 including IL-12, IL-4, IL-6, IL-10, IL-8 and TNF-beta as optimal for
 classifying the LNTB status of an individual. For the sake of clinical
 applicability we further selected a three analyte panel (IL-8, IL-10 and
 TNF-beta ) which was subjected to multinomial modeling in the independent
 validation cohort which was randomised into training and test cohorts,
 achieving an overwhelming 95.9% overall classifying accuracy for correctly
 classifying LNTB cases with a minimal (7%) misclassification error rate in
 the test cohort. Conclusions: In our study, a three analyte serum
 biosignatures and probability equations were established which can guide
 the physician in their clinical decision making and step wise management
 of LNTB patients. This set of biomarkers has the potential to be a
 valuable adjunct to the diagnosis of TL in cases where AFB positivity and
 granulomatous findings elude the clinician.
description: Serum cytokine Raw Data
 for open accessThe data presented is
 the raw cytokine levels expressed in pg/ml. Sheet 1 is the data for 12
 cytokines for the derivation cohort; Sheet 2 is the data for 3 cytokines
 for the validation cohort; Sheet 3 has data for 3 cytokines before and
 after ATT treatment.Data for open
 access.xlsx