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

Biomarkers. 2015;20(6-7):502-12. doi: 10.3109/1354750X.2015.1094141. Epub 2015 Oct 16.

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.

Keywords: Chemokines; HAM/TSP; HTLV-1; cytokines and morbidity; leukotrienes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Blotting, Western
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HTLV-I Infections / blood*
  • HTLV-I Infections / immunology
  • HTLV-I Infections / virology
  • Host-Pathogen Interactions / immunology
  • 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
  • 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

Substances

  • Biomarkers
  • Chemokine CXCL10
  • Inflammation Mediators
  • Interleukin-6
  • Receptors, Leukotriene
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Leukotriene B4
  • Interleukin-4
  • Interferon-gamma
  • leukotriene D4 receptor