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Research article
Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren's syndrome
Tsutomu Takeuchi
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1111-8218
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Arthritis Research & Therapy.
Background. The aim of this study was to identify the molecular mechanism of dysregulation of B cell subpopulations of primary Sjögren's syndrome (pSS) at the transcriptome level.
Methods. We enrolled patients with pSS (n=6) and healthy controls (HC) (n=6) in the discovery cohort using microarray and pSS (n=14) and HC (n=12) in the validation cohort using quantitative PCR (qPCR). Peripheral B cells acquired from these subjects were separated by cell sorting into four subsets: CD38-IgD+ (Bm1), CD38+IgD+ (naïve B cells), CD38highIgD+ (pre-germinal centre B cells) and CD38±IgD- (memory B cells). We performed differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA).
Results. Expression of the long non-coding RNA LINC00487 was significantly upregulated in all B cell subsets, as was that of HLA and interferon (IFN) signature genes. Moreover, the normalized intensity value of LINC00487 significantly correlated with the disease activity score of all pSS B cell subsets. Studies of human B cell lines revealed that the expression of LINC00487 was strongly induced by IFNα. WGCNA revealed six gene clusters associated with the B cell subpopulation of pSS. Further, SOX4 was identified as an inter-module hub gene.
Conclusion. Our transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS.
Keywords
primary Sjögren's syndrome, B cells, long non-coding RNA, transcriptome, gene co-expression network
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Posted 13 Jun, 2020
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On 22 Jun, 2020
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On 10 Jun, 2020
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On 09 Jun, 2020
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On 09 Jun, 2020
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Received 08 Jun, 2020
Editorial decision: Minor revision
On 08 Jun, 2020
Editor assigned
On 01 Jun, 2020
Reviewers invited
Invitations sent on 01 Jun, 2020
Reviewer #1 agreed
On 01 Jun, 2020
Submission checks complete
On 31 May, 2020
Editor invited
On 31 May, 2020
No comments provided
Editorial decision: Major revision
On 22 May, 2020
Review #2 received
Received 17 May, 2020
Review #1 received
Received 05 May, 2020
Reviewer #1 agreed
On 04 May, 2020
Reviewer #2 agreed
On 04 May, 2020
Reviewers invited
Invitations sent on 04 May, 2020
Editor assigned
On 30 Apr, 2020
First submitted
On 29 Apr, 2020
Submission checks complete
On 29 Apr, 2020
Editor invited
On 29 Apr, 2020
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Subject Areas
Rheumatology
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This preprint is under consideration at Arthritis Research & Therapy. 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
Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren's syndrome
Tsutomu Takeuchi
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1111-8218
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
Version 3
Posted 13 Jun, 2020
Published
On 22 Jun, 2020
No community comments so far
Editor assigned
On 10 Jun, 2020
Submission checks complete
On 09 Jun, 2020
Editor invited
On 09 Jun, 2020
No comments provided
Review #1 received
Received 08 Jun, 2020
Editorial decision: Minor revision
On 08 Jun, 2020
Editor assigned
On 01 Jun, 2020
Reviewers invited
Invitations sent on 01 Jun, 2020
Reviewer #1 agreed
On 01 Jun, 2020
Submission checks complete
On 31 May, 2020
Editor invited
On 31 May, 2020
No comments provided
Editorial decision: Major revision
On 22 May, 2020
Review #2 received
Received 17 May, 2020
Review #1 received
Received 05 May, 2020
Reviewer #1 agreed
On 04 May, 2020
Reviewer #2 agreed
On 04 May, 2020
Reviewers invited
Invitations sent on 04 May, 2020
Editor assigned
On 30 Apr, 2020
First submitted
On 29 Apr, 2020
Submission checks complete
On 29 Apr, 2020
Editor invited
On 29 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Arthritis Research & Therapy.
Background. The aim of this study was to identify the molecular mechanism of dysregulation of B cell subpopulations of primary Sjögren's syndrome (pSS) at the transcriptome level.
Methods. We enrolled patients with pSS (n=6) and healthy controls (HC) (n=6) in the discovery cohort using microarray and pSS (n=14) and HC (n=12) in the validation cohort using quantitative PCR (qPCR). Peripheral B cells acquired from these subjects were separated by cell sorting into four subsets: CD38-IgD+ (Bm1), CD38+IgD+ (naïve B cells), CD38highIgD+ (pre-germinal centre B cells) and CD38±IgD- (memory B cells). We performed differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA).
Results. Expression of the long non-coding RNA LINC00487 was significantly upregulated in all B cell subsets, as was that of HLA and interferon (IFN) signature genes. Moreover, the normalized intensity value of LINC00487 significantly correlated with the disease activity score of all pSS B cell subsets. Studies of human B cell lines revealed that the expression of LINC00487 was strongly induced by IFNα. WGCNA revealed six gene clusters associated with the B cell subpopulation of pSS. Further, SOX4 was identified as an inter-module hub gene.
Conclusion. Our transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5