Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP

Abstract Background Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-...

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Main Authors: Bárbara Brasil Santana, Maria Alice Freitas Queiroz, Rodrigo Arcoverde Cerveira, Claudia Mendonça Rodrigues, Ednelza da Silva Graça Amoras, Carlos Araújo da Costa, Maisa Silva de Sousa, Ricardo Ishak, Luiz Ricardo Goulart, Antonio Carlos Rosário Vallinoto
Format: Article
Language:English
Published: BMC 2021-02-01
Series:BMC Infectious Diseases
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Online Access:https://doi.org/10.1186/s12879-021-05917-y
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author Bárbara Brasil Santana
Maria Alice Freitas Queiroz
Rodrigo Arcoverde Cerveira
Claudia Mendonça Rodrigues
Ednelza da Silva Graça Amoras
Carlos Araújo da Costa
Maisa Silva de Sousa
Ricardo Ishak
Luiz Ricardo Goulart
Antonio Carlos Rosário Vallinoto
author_facet Bárbara Brasil Santana
Maria Alice Freitas Queiroz
Rodrigo Arcoverde Cerveira
Claudia Mendonça Rodrigues
Ednelza da Silva Graça Amoras
Carlos Araújo da Costa
Maisa Silva de Sousa
Ricardo Ishak
Luiz Ricardo Goulart
Antonio Carlos Rosário Vallinoto
author_sort Bárbara Brasil Santana
collection DOAJ
description Abstract Background Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients. Methods This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Results ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000). Conclusions Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.
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spelling doaj.art-19274ab3ddfe44f9a3d6e485b718bac12022-12-21T22:53:13ZengBMCBMC Infectious Diseases1471-23342021-02-012111810.1186/s12879-021-05917-yLow Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSPBárbara Brasil Santana0Maria Alice Freitas Queiroz1Rodrigo Arcoverde Cerveira2Claudia Mendonça Rodrigues3Ednelza da Silva Graça Amoras4Carlos Araújo da Costa5Maisa Silva de Sousa6Ricardo Ishak7Luiz Ricardo Goulart8Antonio Carlos Rosário Vallinoto9Laboratório de Virologia, Instituto de Ciências Biológica, Universidade Federal do ParáLaboratório de Virologia, Instituto de Ciências Biológica, Universidade Federal do ParáLaboratório de Virologia, Instituto de Ciências Biológica, Universidade Federal do ParáLaboratory of Nanobiotechnology, Biotechnology Institute, Federal University of UberlândiaLaboratório de Virologia, Instituto de Ciências Biológica, Universidade Federal do ParáLaboratory of Cellular and Molecular Biology, Tropical Medicine Center, Federal University of ParáLaboratory of Cellular and Molecular Biology, Tropical Medicine Center, Federal University of ParáLaboratório de Virologia, Instituto de Ciências Biológica, Universidade Federal do ParáLaboratory of Nanobiotechnology, Biotechnology Institute, Federal University of UberlândiaLaboratório de Virologia, Instituto de Ciências Biológica, Universidade Federal do ParáAbstract Background Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients. Methods This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Results ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000). Conclusions Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.https://doi.org/10.1186/s12879-021-05917-yAnnexin A1HTLVHAM/TSPInfectionBiomarker
spellingShingle Bárbara Brasil Santana
Maria Alice Freitas Queiroz
Rodrigo Arcoverde Cerveira
Claudia Mendonça Rodrigues
Ednelza da Silva Graça Amoras
Carlos Araújo da Costa
Maisa Silva de Sousa
Ricardo Ishak
Luiz Ricardo Goulart
Antonio Carlos Rosário Vallinoto
Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP
BMC Infectious Diseases
Annexin A1
HTLV
HAM/TSP
Infection
Biomarker
title Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP
title_full Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP
title_fullStr Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP
title_full_unstemmed Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP
title_short Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP
title_sort low annexin a1 level in htlv 1 infected patients is a potential biomarker for the clinical progression and diagnosis of ham tsp
topic Annexin A1
HTLV
HAM/TSP
Infection
Biomarker
url https://doi.org/10.1186/s12879-021-05917-y
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