Objective We constructed a gene coexpression network to uncover central key genes related to Sjögren’s disease (SjD), and investigated the clinical significance of bone marrow stromal antigen 2 (BST2) in SjD. Methods Two microarray datasets (GSE84844 and GSE66795) were analyzed to construct a gene coexpression network and identify hub genes, using the GSE51092 dataset for validation. The expression of the hub gene BST2 in peripheral blood mononuclear cells (PBMCs) was quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR), and BST2 expression on T cells subsets was measured using flow cytometry in 35 SjD and 20 healthy controls (HC). Furthermore, we analyzed the correlations between the proportion of BST2 + CD4 + T cells and various clinical and laboratory features. Results Sixteen hub genes (BST2, IFI27, IFI6, PARP12, HERC6, PLSCR1, LY6E, EIF2AK2, GBP1, IFI44L, RTP4, IFIT2, MX1, OASL, GBP5, and XAF1) were identified through WGCNA. BST2 mRNA expression showed significantly elevated in SjD than HC (p < 0.05). Compared to HC, the proportions of BST2 + cells were markedly higher among the CD3 + , CD4 + , and CD8 + T cell subsets in SjD (p < 0.05). The proportion of BST2 + CD4 + T cells was positively associated with serum IgG and ESR and negatively associated with serum C3 (all p < 0.05). BST2 + CD4 + T cells proportions were more greater in patients with ≥ 2 involved organ systems, fatigue, anemia, interstitial lung disease, high IgG levels, or rheumatoid factor positivity than in those without these manifestations (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the proportion of BST2 + CD4 + T cells was good for the diagnosis and disease activity of SjD. Conclusions These findings suggest that BST2 may serve as a potential biomarker for identifying and evaluating disease activity of SjD, but further investigattion of this biomarker in SjD is needed.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="justify" colname="c1" colnum="1" /> <colspec align="justify" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> Key Points • Compared with that in HC, the mRNA expression of BST2 in SjD significantly increased. • The proportion of BST2+CD4+ T cells was elevated in SjD, especially among those with active disease and multi-system involvement. • The proportion of BST2+CD4+ T cells was good for diagnosing and evaluating the disease activity of SjD. </entry> </row> </tbody> </tgroup> </Table>

Elevated proportion of BST2 + CD4 + T cells: a potential biomarker for diagnosis and disease activity in Sjögren’s disease

期刊论文
发表日期：

2026年4月9日

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Tian Ren,
Xin Zhou,
Erye Zhou,
Cuiping Liu,
Jian Wu,
Xin Chang,
Weichang Chen

摘要

Objective

We constructed a gene coexpression network to uncover central key genes related to Sjögren’s disease (SjD), and investigated the clinical significance of bone marrow stromal antigen 2 (BST2) in SjD.

Methods

Two microarray datasets (GSE84844 and GSE66795) were analyzed to construct a gene coexpression network and identify hub genes, using the GSE51092 dataset for validation. The expression of the hub gene BST2 in peripheral blood mononuclear cells (PBMCs) was quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR), and BST2 expression on T cells subsets was measured using flow cytometry in 35 SjD and 20 healthy controls (HC). Furthermore, we analyzed the correlations between the proportion of BST2 + CD4 + T cells and various clinical and laboratory features.

Results

Sixteen hub genes (BST2, IFI27, IFI6, PARP12, HERC6, PLSCR1, LY6E, EIF2AK2, GBP1, IFI44L, RTP4, IFIT2, MX1, OASL, GBP5, and XAF1) were identified through WGCNA. BST2 mRNA expression showed significantly elevated in SjD than HC (p < 0.05). Compared to HC, the proportions of BST2 + cells were markedly higher among the CD3 + , CD4 + , and CD8 + T cell subsets in SjD (p < 0.05). The proportion of BST2 + CD4 + T cells was positively associated with serum IgG and ESR and negatively associated with serum C3 (all p < 0.05). BST2 + CD4 + T cells proportions were more greater in patients with ≥ 2 involved organ systems, fatigue, anemia, interstitial lung disease, high IgG levels, or rheumatoid factor positivity than in those without these manifestations (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the proportion of BST2 + CD4 + T cells was good for the diagnosis and disease activity of SjD.

Conclusions

These findings suggest that BST2 may serve as a potential biomarker for identifying and evaluating disease activity of SjD, but further investigattion of this biomarker in SjD is needed.

Key Points

• Compared with that in HC, the mRNA expression of BST2 in SjD significantly increased.

• The proportion of BST2+CD4+ T cells was elevated in SjD, especially among those with active disease and multi-system involvement.

• The proportion of BST2+CD4+ T cells was good for diagnosing and evaluating the disease activity of SjD.