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Background: Ischemic stroke, such as transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI) , are the serious problems in the aging society. Therefore, development of biomarkers for TIA and aCI are attempted.
Methods: Candidate antigens recognized by IgG autoantibodies in the serum of 19 TIA patients were screened by a human aortic endothelial cell cDNA library. Serum antibody levels against the antigens were examined by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in healthy donor (HD), TIA, and aCI cohorts ( n = 285, 92 and 529). The antibody levels in the sera of the Japan Public Health Center-based Prospective Cohort Study (JPHC) from 1991 to 1993 was also examined.
Results: Aldolase A, fructose-bisphosphate (ALDOA) and fumarate hydratase (FH) were identified as the candidate antigens. AlphaLISA revealed that the levels of anti-ALDOA antibodies (ALDOA-Abs) and anti-FH antibodies (FH-Abs) were both higher in patients with TIA or aCI than those in HDs ( P < 0.05). The levels of ALDOA-Abs [odds ratio (OR): 2.46, P = 0.0050] and FH-Abs (OR: 2.49, P = 0.0037) were independent predictors of TIA by multivariate logistic regression analysis. The case-control study showed the levels of ALDOA-Abs (OR: 2.50, P < 0.01) and FH-abs (OR: 2.60, P < 0.01) were associated with risk of aCI. Correlation analysis demonstrated that both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease and habitual smoking. These antibody levels were also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis.
Conclusions: ALDOA-Abs and FH-Abs can serve as novel potential biomarkers for prediction of atherosclerotic TIA and aCI.
Keywords
transient ischemic attack, cerebral infarction, ALDOA, FH, antibody biomarker
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CURRENT STATUS: Published
View the published article at BMC Neurology.
Version 2
Posted 31 Aug, 2020
No community comments so far
Editorial decision: Minor revision
On 08 Apr, 2021
Review #2 received
Received 07 Apr, 2021
Reviewer #2 agreed
On 16 Mar, 2021
Review #1 received
Received 09 Sep, 2020
Reviewers invited
Invitations sent on 30 Aug, 2020
Reviewer #1 agreed
On 30 Aug, 2020
Editor assigned
On 27 Aug, 2020
Submission checks complete
On 26 Aug, 2020
Editor invited
On 26 Aug, 2020
No comments provided
Editorial decision: Major revision
On 08 Jul, 2020
Review #2 received
Received 06 May, 2020
Review #1 received
Received 06 May, 2020
Reviewer #2 agreed
On 24 Apr, 2020
Reviewer #1 agreed
On 07 Apr, 2020
Reviewers invited
Invitations sent on 31 Mar, 2020
First submitted
On 18 Mar, 2020
Editor assigned
On 18 Mar, 2020
Submission checks complete
On 17 Mar, 2020
Editor invited
On 17 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurology
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A new preprint design is coming!
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See the published version of this preprint at BMC Neurology.
This is a preprint, 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
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: Published
View the published article at BMC Neurology.
Version 2
Posted 31 Aug, 2020
No community comments so far
Editorial decision: Minor revision
On 08 Apr, 2021
Review #2 received
Received 07 Apr, 2021
Reviewer #2 agreed
On 16 Mar, 2021
Review #1 received
Received 09 Sep, 2020
Reviewers invited
Invitations sent on 30 Aug, 2020
Reviewer #1 agreed
On 30 Aug, 2020
Editor assigned
On 27 Aug, 2020
Submission checks complete
On 26 Aug, 2020
Editor invited
On 26 Aug, 2020
No comments provided
Editorial decision: Major revision
On 08 Jul, 2020
Review #2 received
Received 06 May, 2020
Review #1 received
Received 06 May, 2020
Reviewer #2 agreed
On 24 Apr, 2020
Reviewer #1 agreed
On 07 Apr, 2020
Reviewers invited
Invitations sent on 31 Mar, 2020
First submitted
On 18 Mar, 2020
Editor assigned
On 18 Mar, 2020
Submission checks complete
On 17 Mar, 2020
Editor invited
On 17 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Neurology.
Background: Ischemic stroke, such as transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI) , are the serious problems in the aging society. Therefore, development of biomarkers for TIA and aCI are attempted.
Methods: Candidate antigens recognized by IgG autoantibodies in the serum of 19 TIA patients were screened by a human aortic endothelial cell cDNA library. Serum antibody levels against the antigens were examined by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in healthy donor (HD), TIA, and aCI cohorts ( n = 285, 92 and 529). The antibody levels in the sera of the Japan Public Health Center-based Prospective Cohort Study (JPHC) from 1991 to 1993 was also examined.
Results: Aldolase A, fructose-bisphosphate (ALDOA) and fumarate hydratase (FH) were identified as the candidate antigens. AlphaLISA revealed that the levels of anti-ALDOA antibodies (ALDOA-Abs) and anti-FH antibodies (FH-Abs) were both higher in patients with TIA or aCI than those in HDs ( P < 0.05). The levels of ALDOA-Abs [odds ratio (OR): 2.46, P = 0.0050] and FH-Abs (OR: 2.49, P = 0.0037) were independent predictors of TIA by multivariate logistic regression analysis. The case-control study showed the levels of ALDOA-Abs (OR: 2.50, P < 0.01) and FH-abs (OR: 2.60, P < 0.01) were associated with risk of aCI. Correlation analysis demonstrated that both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease and habitual smoking. These antibody levels were also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis.
Conclusions: ALDOA-Abs and FH-Abs can serve as novel potential biomarkers for prediction of atherosclerotic TIA and aCI.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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