Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy pati
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ESEARCH ARTICLE
Open Access
Functional biomarker signatures of circulating T‑cells and its association with distinct clinical status of leprosy patients and their respective household contacts Pedro Henrique Ferreira Marçal1*†, Rafael Silva Gama1, Lorena Bruna Pereira de Oliveira1, Olindo Assis Martins‑Filho2, Roberta Olmo Pinheiro3, Euzenir Nunes Sarno3, Milton Ozório Moraes3 and Lucia Alves de Oliveira Fraga4*†
Abstract Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes: pauci‑ bacillary (PB) and multibacillary (MB), closely related to the host immune responses. In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household contacts. Methods: The cross-sectional study enrolled 49 participants, including 19 patients and 30 healthy controls. Periph‑ eral blood mononuclear cells (PBMC) were isolated and incubated in the presence of Mycobacterium leprae bacilli. The cells were prepared for surface (CD4+ and CD8+) and intracytoplasmic cytokine staining (IFN-γ, IL-4 and IL-10). Multiple comparisons amongst groups were carried out by ANOVA, Kruskal–Wallis, Student T or Mann–Whitney test. Comparative analysis of categorical variables was performed by Chi-square. Functional biomarker signature analysis was conducted using the global median values for each biomarker index as the cut-off edge to identify the propor‑ tion of subjects with high biomarker levels. Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets, with increased frequency of IFN-γ+ T-cell subsets along with IL-10+ and IL-4+ from CD4+ T-cells, as compared to health Controls (Venn diagram report). Moreover, statistical analysis was carried out using parametric or non-parametric variance analysis followed by pairwise multiple comparisons, according to the data normality distribution. L(PB) displayed a polyfunctional profile characterized by enhanced percentage of IFN-γ+, IL-10+ and IL-4+ produced by most T-cell subsets, as compared to L(MB) that presented a more restricted cytokine functional profile mediated by IL-10+ and IL-4+ T-cells with minor contribution of IFN-γ produced by CD4+ T-cells. Noteworthy was that
*Correspondence: [email protected]; [email protected]; [email protected]; [email protected] † Pedro Henrique Ferreira Marçal and Lucia Alves de Oliveira Fraga shared the co-seniorship 1 Universidade Vale do Rio Doce – Univale, Governador Valadares, MG, Brazil 4 Núcleo de Pesquisa em Hansenologia, Universidade Federal de Juiz de Fora, Instituto de Ciências da Vida, Campus Governador Valadares, Rua São Paulo, 582 – Centro, Governador Valadares, MG 30190‑002, Brazil Full list of author information is available at the end of the article © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permi
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