Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren's syndrome
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.
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Posted 13 Jun, 2020
On 22 Jun, 2020
On 10 Jun, 2020
On 09 Jun, 2020
On 09 Jun, 2020
Received 08 Jun, 2020
On 08 Jun, 2020
On 01 Jun, 2020
Invitations sent on 01 Jun, 2020
On 01 Jun, 2020
On 31 May, 2020
On 31 May, 2020
On 22 May, 2020
Received 17 May, 2020
Received 05 May, 2020
On 04 May, 2020
On 04 May, 2020
Invitations sent on 04 May, 2020
On 30 Apr, 2020
On 29 Apr, 2020
On 29 Apr, 2020
On 29 Apr, 2020
Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren's syndrome
Posted 13 Jun, 2020
On 22 Jun, 2020
On 10 Jun, 2020
On 09 Jun, 2020
On 09 Jun, 2020
Received 08 Jun, 2020
On 08 Jun, 2020
On 01 Jun, 2020
Invitations sent on 01 Jun, 2020
On 01 Jun, 2020
On 31 May, 2020
On 31 May, 2020
On 22 May, 2020
Received 17 May, 2020
Received 05 May, 2020
On 04 May, 2020
On 04 May, 2020
Invitations sent on 04 May, 2020
On 30 Apr, 2020
On 29 Apr, 2020
On 29 Apr, 2020
On 29 Apr, 2020
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