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Research Article
Low Annexin A1 level in HTLV-1 Infected Patients might be a Potential Biomarker for the Clinical Progression and Diagnosis of HAM/TSP
Antonio Carlos Vallinoto
Federal University of Para
Corresponding Author
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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=1,000).
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.
Keywords
Annexin A1, HTLV, HAM/TSP, Infection, Biomarker
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On 25 Dec, 2020
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On 25 Dec, 2020
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On 25 Dec, 2020
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On 25 Dec, 2020
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This preprint is under consideration at BMC Infectious Diseases. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Low Annexin A1 level in HTLV-1 Infected Patients might be a Potential Biomarker for the Clinical Progression and Diagnosis of HAM/TSP
Antonio Carlos Vallinoto
Federal University of Para
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 29 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 21 Jan, 2021
Review #3 received
Received 20 Jan, 2021
Review #2 received
Received 20 Jan, 2021
Reviewer #4 agreed
On 31 Dec, 2020
Reviewer #6 agreed
On 31 Dec, 2020
Reviewer #5 agreed
On 31 Dec, 2020
Review #13 received
Received 30 Dec, 2020
Review #9 received
Received 30 Dec, 2020
Review #10 received
Received 30 Dec, 2020
Review #12 received
Received 30 Dec, 2020
Review #7 received
Received 30 Dec, 2020
Review #1 received
Received 30 Dec, 2020
Review #11 received
Received 30 Dec, 2020
Review #5 received
Received 30 Dec, 2020
Review #8 received
Received 30 Dec, 2020
Review #6 received
Received 30 Dec, 2020
Reviewer #15 agreed
On 25 Dec, 2020
Reviewer #2 agreed
On 25 Dec, 2020
Reviewer #11 agreed
On 25 Dec, 2020
Reviewer #12 agreed
On 25 Dec, 2020
Reviewer #14 agreed
On 25 Dec, 2020
Reviewer #9 agreed
On 25 Dec, 2020
Reviewer #3 agreed
On 25 Dec, 2020
Reviewer #13 agreed
On 25 Dec, 2020
Reviewer #7 agreed
On 25 Dec, 2020
Reviewer #1 agreed
On 25 Dec, 2020
Reviewer #10 agreed
On 25 Dec, 2020
Reviewer #8 agreed
On 25 Dec, 2020
Reviewers invited
Invitations sent on 25 Dec, 2020
Editor assigned
On 25 Dec, 2020
Editor invited
On 24 Dec, 2020
Submission checks complete
On 24 Dec, 2020
First submitted
On 18 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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=1,000).
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.
Figure 1
Figure 2
Figure 3
Figure 4
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and accessed as a PDF.