Vascular endothelial growth factor (VEGF) and interleukin-1 receptor antagonist (IL-1Ra) as promising biomarkers for distinguishing active from latent tuberculosis in children and adolescents - 28/05/22

Doi : 10.1016/j.tube.2022.102205

Camila de Paula Martins ^a,^{^{1
These authors contributed equally to the paper.}}, Fabiana Rabe Carvalho ^a,^{^{1
These authors contributed equally to the paper.}}, Renan Faustino ^a, Thalia Medeiros ^a,^b, Natalia Fonseca do Rosário ^a, Christiane Mello Schmidt ^a,^c, Ana Paula Barbosa ^d, Ana Paula Quintanilha dos Santos ^e, Caio Pluvier Duarte Costa ^a, Hugo Henrique Kegler dos Santos ^f, Karina Yuriko Yaginuma ^f, Elisangela Costa da Silva ^g, Afranio Lineu Kritski ^g, Clemax Couto Sant’Anna ^g, Claudete Aparecida Araújo Cardoso ^a,^c,^⁎ , Andrea Alice Silva ^a,^b,^⁎
^a Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil
^b Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil
^c Departamento Materno-Infantil, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil
^d Programa de Controle de Tuberculose da Secretaria de Saúde de São Gonçalo, Rio de Janeiro, Brazil
^e Programa de Controle de Tuberculose da Secretaria de Saúde de Itaboraí, Rio de Janeiro, Brazil
^f Departamento de Estatística, Instituto de Matemática e Estatística, Universidade Federal Fluminense, Rio de Janeiro, Brazil
^g Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

^∗Corresponding author. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Universidade Federal Fluminense. 303 Marques do Paraná Avenue, 24033900; Niterói - Rio de Janeiro, Brazil.Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências MédicasFaculdade de MedicinaUniversidade Federal Fluminense303 Marques do Paraná Avenue, 24033900; NiteróiRio de JaneiroBrazil^∗∗Corresponding author. Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brazil.Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências MédicasFaculdade de MedicinaUniversidade Federal FluminenseRio de JaneiroBrazil

Abstract

Since distinguishing pulmonary (PTB) from latent tuberculosis (LTBI) in pediatric patients remains a challenge, we aimed to investigate the efficacy of immune mediators in diagnosing PTB and LTBI in this population. In this cross-sectional study performed with children and adolescents, serum levels of 20 biomarkers were assessed and data were analyzed according to age groups. We included 65 participants (PTB, n = 28 and LTBI, n = 37). Overall, levels of TNF-α, IL-1Ra, IL-6, IL-17A, VEGF, MMP-1, and procalcitonin were significantly higher (P < 0.05) in adolescents and children <10 years-old with PTB. Also, principal component analysis (PCA) showed that immune mediators were able to distinguish PTB from LTBI. VEGF and IL-1Ra presented the highest area under the curve (AUC) values, both separately (AUC 0.890 and 0.785) and combined (AUC 0.99). Taken together, we showed that VEGF and IL-1Ra are promising biomarkers to distinguish PTB from LTBI in pediatric patients, especially in children <5 years-old.

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Highlights

•	Diagnosing pulmonary and latent tuberculosis (PTB/LTBI) in children is a challenge.
•	Children with PTB showed higher levels of immune mediators.
•	VEGF and IL-1Ra are promising biomarkers to and distinguish PTB from ILTB.

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Keywords : Tuberculosis, Inflammatory mediators, VEGF, IL-1Ra, Children, Adolescents

Plan

Introduction

Patients and methods

TB diagnosis

Data collection and blood sampling

Assessment of inflammatory mediators

Statistical analysis

Results

Clinical and demographic characteristic of children and adolescents

Assessment of circulating inflammatory mediators in children and adolescents with PTB and LTBI

ROC curves revealed differences between LTBI and PTB in children and adolescents

ROC curve revealed differences between LTBI and PTB in children under five years-old

Discussion

Conclusion

Author’s contributions

Funding

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Article 102205- mai 2022 Retour au numéro

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Vascular endothelial growth factor (VEGF) and interleukin-1 receptor antagonist (IL-1Ra) as promising biomarkers for distinguishing active from latent tuberculosis in children and adolescents - 28/05/22

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