Abstract: FR-PO1032
Alterations in Frequency and Function Exhausted Memory B Cells in Lupus Nephritis and Systemic Lupus Erythematosus
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Zhu, Litong, Queen Mary Hospital, Hong Kong, HongKong, Hong Kong
- Yap, Yat Hin Desmond, Queen Mary Hospital, Hong Kong, HongKong, Hong Kong
Background
Various B cell abnormalities have been implicated in the pathogenesis of LN, and our previous studies have demonstrated that memory B cells assume pathogenic relevance in disease relapse. Exhausted B cell is a B lymphocyte aberration initially reported in HIV infection, and was also observed in autoimmune disorders. The pathogenic roles of exhausted B cells in LN and disease relapse remains unclear.
Methods
Classical memory (CD19+CD21+CD27+) and exhausted B cells (CD19+CD21–CD27–) were measured in LN patients with multiple relapses (MR) (n=12) or no relapse (NR) (n=12) during disease remission. B cell-related cytokines, homing and inhibitory receptors, proliferation and calcium mobilization in classical and exhausted memory B cells were also assessed. Using single-cell RNA sequencing data from NIH and GEO, we also performed bioinformatics analysis to identify genes and pathways relevant to memory and exhausted B cells in SLE, LN and healthy controls.
Results
The MR group exhibited higher proportion of circulating exhausted B cells compared to NR (16.7 ± 9.5% vs 10.5 ± 5.7%, p <0.05). Blood levels of IL-6, BAFF and IL-21 in MR patients were higher than the NR group (75.1 ± 37.2 vs 33.6 ± 14.2 pg/ml; 1491.1 ± 680.9 vs 1120.1 ± 384.1 pg/ml and 23.5 ± 23.0 vs 5.1 ± 3.1 pg/ml respectively; p<0.05, for all) . The MR had higher blood levels of Siglec-6, CXCR3 and CD62L than the NR group (2.6 ± 0.8 vs 1.3 ± 0.6 ng/ml; 2.3 ± 1.4 vs 1.6 ± 0.8 ng/ml; 3240.9 ± 1002.0 vs 2497.0 ± 671.8 ng/ml respectively, p＜0.05 for all) . Expression of inhibitory receptors CD22, CD85j, CD183 and FCRL4 in exhausted B cells were increased in the MR group compared to the NR group. Exhausted B cells from MR patients also showed decreased proliferation compared to NR patients (1.9 ± 1.1% vs 3.8 ± 1.3%, p<0.05) and impaired calcium mobilization in response to B-cell receptor triggering. STAT1, XAF1, MX1, IFI44L,EPSTI1,LCP1,OAS1, NEAT1, IFI16, IFI44 in exhausted B cells and XAF1,MX1, IFI44L in memory B cells play a pathogenic role in LN patients. SLE patient also show increased proportion of exhausted B cells compared to healthy control and the expression of STAT1, XAF1, MX1, IFI44L correlate positively with the proportion of exhausted B cells.
Conclusion
Our results suggested that altered numbers and function of exhausted B cells may have pathogenic significance in SLE and LN.
Funding
- Government Support – Non-U.S.