Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progression
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 plasm...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2021-10-01
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| Series: | Therapeutic Advances in Chronic Disease |
| Online Access: | https://doi.org/10.1177/20406223211048644 |
| _version_ | 1818729098104537088 |
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| author | Youxia Liu Huyan Yu Sijing Wu Xia Yang Congcong Cao Fanghao Wang Junya Jia Tiekun Yan |
| author_facet | Youxia Liu Huyan Yu Sijing Wu Xia Yang Congcong Cao Fanghao Wang Junya Jia Tiekun Yan |
| author_sort | Youxia Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T22:40:29Z |
| format | Article |
| id | doaj.art-44c02fb238ed41e5a540281568e5041c |
| institution | Directory Open Access Journal |
| issn | 2040-6231 |
| language | English |
| last_indexed | 2024-12-17T22:40:29Z |
| publishDate | 2021-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Chronic Disease |
| spelling | doaj.art-44c02fb238ed41e5a540281568e5041c2022-12-21T21:29:56ZengSAGE PublishingTherapeutic Advances in Chronic Disease2040-62312021-10-011210.1177/20406223211048644Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progressionYouxia LiuHuyan YuSijing WuXia YangCongcong CaoFanghao WangJunya JiaTiekun YanBackground: 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.https://doi.org/10.1177/20406223211048644 |
| spellingShingle | Youxia Liu Huyan Yu Sijing Wu Xia Yang Congcong Cao Fanghao Wang Junya Jia Tiekun Yan Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progression Therapeutic Advances in Chronic Disease |
| title | Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progression |
| title_full | Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progression |
| title_fullStr | Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progression |
| title_full_unstemmed | Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progression |
| title_short | Plasma ST6GAL1 regulates IgG sialylation to control IgA nephropathy progression |
| title_sort | plasma st6gal1 regulates igg sialylation to control iga nephropathy progression |
| url | https://doi.org/10.1177/20406223211048644 |
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