Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progression

Therapeutic Advances in Chronic Disease - Tập 12 - Trang 204062232110486 - 2021
Youxia Liu1, Huyan Yu2, Shidi Wu2, Yang Xia2, Congcong Cao3, Fanghao Wang2, Junya Jia1, Tiekun Yan2
1Department of Nephrology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, P.R. China
2Department of Nephrology, Tianjin Medical University General Hospital, Tianjin, P.R. China
3Hematology Department, The People's Hospital of Pingyi County, Linyi, P.R. China

Tóm tắt

Background: Our previous study revealed that plasma levels of a-2,6-sialyltransferase 1 (ST6GAL1) were increased in patients with IgA nephropathy (IgAN). ST6GAL1 catalyzes terminal sialylation of IgG to shift the antibody effector function to the anti-inflammatory pattern. However, the role of plasma ST6GAL1 in the progression of IgAN and underlying mechanisms are still unknown. Methods: A total of 180 IgAN patients were included. The kidney outcomes were defined as the eGFR decline or proteinuria remission. Peripheral blood mononuclear cells (PBMCs) were either stimulated with purified sialylated IgG (SA-IgG) or with non-sialylated IgG (NSA-IgG) from IgAN patients to detect the levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in supernatant. Results: Compared with the lower ST6GAL1 (reference), the risk of eGFR decline decreased for the higher ST6GAL1 group after adjustment for baseline eGFR, systolic blood pressure (SBP), and proteinuria. The results showed that patients with higher ST6GAL1 levels had a higher rate of proteinuria remission. ST6GAL1, expressed as a continuous variable, was a protective factor for eGFR decline and proteinuria remission. An in vitro study showed that the administration of recombinant ST6GAL1 (rST6GAL1) decreased the levels of IL-6 and TNF-α in PBMCs. Furthermore, the administration of rST6GAL1 resulted in the enrichment of SA-IgG in a concentration-dependent manner. In addition, as compared to control, purified SA-IgG-treated PBMCs showed a significant decrease in the expression of IL-6 and TNF-α. Conclusion: Our study indicated that elevated ST6GAL1 was associated with a slower progression of IgAN, which may play a protective effect by increasing IgG sialylation to inhibit the production of proinflammatory cytokines in PBMCs.

Từ khóa


Tài liệu tham khảo

10.2215/CJN.01990213

10.1053/j.semdp.2020.03.001

10.2215/CJN.07420716

10.1159/000502579

10.1016/j.yexcr.2019.111670

10.1159/000086035

Premuzic V, 2020, Case Rep Nephrol, 2020, 9480860

10.1074/jbc.M113.512277

10.1159/000045254

10.1159/000489580

10.1038/ncomms8270

10.2215/CJN.13701217

10.1111/jcmm.15664

10.1021/bi901430h

10.1016/j.cell.2017.11.041

10.1186/s13075-018-1586-z

10.1016/j.bbadis.2018.03.018

Alavi A, 2000, J Rheumatol, 27, 1379

10.1007/s11255-016-1386-9

10.1016/j.kint.2017.02.003

10.5551/jat.38612

10.1016/j.imbio.2020.151973

10.2215/CJN.08600718

10.3904/kjim.1994.9.1.1

10.1007/s10875-010-9405-6

10.1136/jnnp-2014-309964

10.1038/ncomms11205

10.3389/fimmu.2018.01183

10.3899/jrheum.110584

Maixnerova D, 2019, PLoS One, 14

10.1016/j.jaut.2021.102593

Thông tin
Thông tin xuất bản

Therapeutic Advances in Chronic Disease

Tập 12

204062232110486

Thông tin tác giả