title: Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity.
abstract: 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.
authors.affiliation: a Centro De Pesquisas René Rachou - FIOCRUZ-Minas , Belo Horizonte, Minas Gerais , Brazil .|b Fundação Centro De Hematologia E Hemoterapia De Minas Gerais - HEMOMINAS , Santa Efigênia, Minas Gerais , Brazil .|c Programa De Pós-Graduação Em Infectologia E Medicina Tropical - Faculdade De Medicina Da Universidade Federal De Minas Gerais , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Ana Lúcia Borges
authors.initials: AL
authors.lastname: Starling
authors.affiliation: a Centro De Pesquisas René Rachou - FIOCRUZ-Minas , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Jordana Grazziela Alves
authors.initials: JG
authors.lastname: Coelho-Dos-Reis
authors.affiliation: a Centro De Pesquisas René Rachou - FIOCRUZ-Minas , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Vanessa
authors.initials: V
authors.lastname: Peruhype-Magalhães
authors.affiliation: c Programa De Pós-Graduação Em Infectologia E Medicina Tropical - Faculdade De Medicina Da Universidade Federal De Minas Gerais , Belo Horizonte, Minas Gerais , Brazil .|d Department of Anatomic Pathology , Medicine School, Federal University of Minas Gerais , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Marcelo Antônio
authors.initials: MA
authors.lastname: Pascoal-Xavier
authors.affiliation: c Programa De Pós-Graduação Em Infectologia E Medicina Tropical - Faculdade De Medicina Da Universidade Federal De Minas Gerais , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Denise Utsch
authors.initials: DU
authors.lastname: Gonçalves
authors.affiliation: a Centro De Pesquisas René Rachou - FIOCRUZ-Minas , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Samantha Ribeiro
authors.initials: SR
authors.lastname: Béla
authors.affiliation: c Programa De Pós-Graduação Em Infectologia E Medicina Tropical - Faculdade De Medicina Da Universidade Federal De Minas Gerais , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Lambertucci
authors.affiliation: c Programa De Pós-Graduação Em Infectologia E Medicina Tropical - Faculdade De Medicina Da Universidade Federal De Minas Gerais , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Ludimila
authors.initials: L
authors.lastname: Labanca
authors.affiliation: c Programa De Pós-Graduação Em Infectologia E Medicina Tropical - Faculdade De Medicina Da Universidade Federal De Minas Gerais , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Silvio Roberto
authors.initials: SR
authors.lastname: Souza Pereira
authors.affiliation: a Centro De Pesquisas René Rachou - FIOCRUZ-Minas , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.affiliation: e Hospital Sarah Kubitschek , Belo Horizonte, Minas Gerais , Brazil , and.
authors.forename: João Gabriel
authors.initials: JG
authors.lastname: Ribas
authors.affiliation: a Centro De Pesquisas René Rachou - FIOCRUZ-Minas , Belo Horizonte, Minas Gerais , Brazil .|f Laboratório De Inflamação E Imunologia Das Parasitoses , Faculdade De Ciências Farmacêuticas De Ribeirão Preto, Universidade De São Paulo , Ribeirão Preto, São Paulo , Brazil.
authors.forename: Bruno Caetano
authors.initials: BC
authors.lastname: Trindade
authors.affiliation: f Laboratório De Inflamação E Imunologia Das Parasitoses , Faculdade De Ciências Farmacêuticas De Ribeirão Preto, Universidade De São Paulo , Ribeirão Preto, São Paulo , Brazil.
authors.forename: Lucia Helena
authors.initials: LH
authors.lastname: Faccioli
authors.affiliation: b Fundação Centro De Hematologia E Hemoterapia De Minas Gerais - HEMOMINAS , Santa Efigênia, Minas Gerais , Brazil .
authors.forename: Anna Bárbara Freitas
authors.initials: AB
authors.lastname: Carneiro-Proietti
authors.affiliation: a Centro De Pesquisas René Rachou - FIOCRUZ-Minas , Belo Horizonte, Minas Gerais , Brazil .
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D015153:Blotting, Western; D054357:Chemokine CXCL10 / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015490:HTLV-I Infections / Q000097:blood* / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood* / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D007975:Leukotriene B4 / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000097:blood* / Q000276:immunology / Q000821:virology; D018077:Receptors, Leukotriene / Q000097:blood / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; D018836:Inflammation Mediators; D015850:Interleukin-6; D018077:Receptors, Leukotriene; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007975:Leukotriene B4; D015847:Interleukin-4; D007371:Interferon-gamma; C083169:leukotriene D4 receptor
keywords: Chemokines; HAM/TSP; HTLV-1; cytokines and morbidity; leukotrienes