Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity

• Published in: Biomarkers Vol. 20; no. 6-7; pp. 502 - 512
• Main Authors: Starling, Ana Lúcia Borges, Coelho-dos-Reis, Jordana Grazziela Alves, Peruhype-Magalhães, Vanessa, Pascoal-Xavier, Marcelo Antônio, Gonçalves, Denise Utsch, Béla, Samantha Ribeiro, Lambertucci, José Roberto, Labanca, Ludimila, Souza Pereira, Silvio Roberto, Teixeira-Carvalho, Andréa, Ribas, João Gabriel, Trindade, Bruno Caetano, Faccioli, Lucia Helena, Carneiro-Proietti, Anna Bárbara Freitas, Martins-Filho, Olindo Assis
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 03-10-2015
• Subjects: Adult; Aged; Biomarkers - blood; Blotting, Western; Chemokine CXCL10 - blood; Chemokine CXCL10 - immunology; Chemokines; cytokines and morbidity; Enzyme-Linked Immunosorbent Assay; Female; HAM/TSP; Host-Pathogen Interactions - immunology; HTLV-1; HTLV-I Infections - blood; HTLV-I Infections - immunology; HTLV-I Infections - virology; Human T-lymphotropic virus 1 - immunology; Human T-lymphotropic virus 1 - physiology; Humans; Inflammation Mediators - blood; Inflammation Mediators - immunology; Interferon-gamma - blood; Interferon-gamma - immunology; Interleukin-10 - blood; Interleukin-10 - immunology; Interleukin-4 - blood; Interleukin-4 - immunology; Interleukin-6 - blood; Interleukin-6 - immunology; Leukotriene B4 - blood; Leukotriene B4 - immunology; leukotrienes; Male; Middle Aged; Paraparesis, Tropical Spastic - blood; Paraparesis, Tropical Spastic - immunology; Paraparesis, Tropical Spastic - virology; Receptors, Leukotriene - blood; Receptors, Leukotriene - immunology; Signal Transduction - immunology; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - immunology; Young Adult; HAM/TSP; HTLV-1; Chemokines; cytokines and morbidity; leukotrienes
• ISSN: 1354-750X; 1366-5804
• DOI: 10.3109/1354750X.2015.1094141

This study aimed at establishing the immunological signature and an algorithm for clinical management of the different clinical stages of the HTLV-1-infection based on serum biomarkers. A panel of serum biomarkers was evaluated by four sets of innovative/non-conventional data analysis approaches in samples from 87 HTLV-1 patients: asymptomatic carriers (AC), putative HTLV-1 associated myelopathy/tropical spastic paraparesis (pHAM/TSP) and HAM/TSP. The analysis of cumulative curves and molecular signatures pointed out that HAM/TSP presented a pro-inflammatory profile mediated by CXCL10/LTB-4/IL-6/TNF-α/IFN-γ, counterbalanced by IL-4/IL-10. The analysis of biomarker networks showed that AC presented a strongly intertwined pro-inflammatory/regulatory net with IL-4/IL-10 playing a central role, while HAM/TSP exhibited overall immune response toward a predominant pro-inflammatory profile. At last, the classification and regression trees proposed for clinical practice allowed for the construction of an algorithm to discriminate AC, pHAM and HAM/TSP patients with the elected biomarkers: IFN-γ, TNF-α, IL-10, IL-6, IL-4 and CysLT. These findings reveal a complex interaction among chemokine/leukotriene/cytokine in HTLV-1 infection and suggest the use of the selected but combined biomarkers for the follow-up/diagnosis of disease morbidity of HTLV-1-infected individuals.