TLR10 expression in unswitched memory B associates with the disease activity of patients with systemic lupus erythematosus

Lumin Zhang; Linchang Yu; Quanfu Li; Meiping Ni; Qiongzhu Dong; Yufang Bao; Jinguan Zhang; Danping Ruan; Zhefeng Meng; Nannan Lai

doi:10.1007/s10067-024-07231-9

TLR10 expression in unswitched memory B associates with the disease activity of patients with systemic lupus erythematosus

Clin Rheumatol. 2024 Nov 14. doi: 10.1007/s10067-024-07231-9. Online ahead of print.

Authors

Lumin Zhang^#¹, Linchang Yu^#², Quanfu Li^#³, Meiping Ni⁴, Qiongzhu Dong¹, Yufang Bao¹, Jinguan Zhang¹, Danping Ruan⁵, Zhefeng Meng⁶, Nannan Lai⁷

Affiliations

¹ Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, 201199, China.
² Department of Intensive Care Unit, Shenzhen University General Hospital, Shenzhen, 518071, China.
³ Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, The Ministry of Education, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
⁴ Department of Scientific Research, Minghang Hospital, Fudan University, Shanghai, 201199, China.
⁵ Department of Stomatology, Minhang Hospital, Fudan University, Shanghai, 201199, China. danping_ruan@fudan.edu.cn.
⁶ Department of Scientific Research, Minghang Hospital, Fudan University, Shanghai, 201199, China. zhefengm@fuduan.edu.cn.
⁷ Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Minhang Hospital, Fudan University, Shanghai, 201199, China. lainn@fudan.edu.cn.

^# Contributed equally.

PMID: 39537946
DOI: 10.1007/s10067-024-07231-9

Abstract

Objective: Systemic lupus erythematosus (SLE) is characterized by impaired B-cell function and a distinct B-cell phenotype. Toll-like receptor (TLR) 10 is highly expressed in human B cells and can regulate B-cell activation. Here, we examined the variations in TLR10 expression across B-cell subpopulations and its impact on the disease activity in SLE patients.

Methods: Thirty-one patients with stable SLE, 30 patients with active SLE, and 28 healthy controls (HCs) were recruited. Flow cytometry was performed to assess the prevalence of B-cell subpopulations and their TLR10 expression. The diagnostic value of unswitched memory B cells (UMB) and double-negative B cells (DNB) in relation to disease activity was determined. The correlations between TLR10 expressions in B-cell subpopulations and disease activity were further evaluated, respectively.

Results: Compared with the HCs, the stable patients exhibited significantly reduced Naive B proportion and elevated switched memory B and DNB proportion, while active patients presented markedly decreased UMB and increased DNB proportion. Furthermore, the receiver operating characteristics analysis revealed that UMB was more reliable than DNB in diagnosing SLE disease activity. Among the B-cell subsets, only the TLR10 expression in UMB was notably diminished in SLE patients, particularly in active patients. Importantly, TLR10 expression in UMB was negatively correlated with the disease activity.

Conclusion: UMB could serve as a promising biomarker for SLE disease activity, and the TLR10 expression in UMB was negatively correlated with the activity of SLE patients, suggesting that TLR10 might be involved in the disease progression of SLE by regulating the UMB function. Key Points • Active SLE patients exhibited reduced unswitched memory B cells and increased double-negative B cell proportions in blood. • Unswitched memory B cells are better predictors of disease activity in SLE than double-negative B cells. • TLR10 expression in unswitched memory B cells is markedly diminished in SLE patients. • TLR10 expression in unswitched memory B cells is negatively associated with SLE disease activity.

Keywords: B cells; Disease activity; Systemic lupus erythematosus; Toll-like receptor 10; Unswitched memory B.

Abstract

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