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.

• Chemokines
• cytokines and morbidity
• HAM/TSP
• HTLV-1
• leukotrienes

Acknowledgment

The authors thank the program for technological development in tools for health-PDTIS-FIOCRUZ for the use of its facilities.

Declaration of interest

The authors report no declarations of interest. This work was supported by FAPEMIG and received technical and financial support from HEMOMINAS, FIOCRUZ and the Graduate Program on Tropical Medicine of the Federal University of Minas Gerais (Programa de Pós-Graduação em Infectologia e Medicina Tropical – Universidade Federal de Minas Gerais – UFMG). O.A.M.F., J.R.L., L.H.F. and A.T.C. are thankful to CNPq for the PQ research fellowship support. J.G.C.-d-R. received fellowship from Programa Nacional de Pós-Doutorado (PNPD/CAPES). This study was conducted with the support of the Grupo Interdisciplinar de Pesquisas em HTLV-1 (GIPH).