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

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. 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. 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. 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.