Sialylation of IgG inhibits the formation of galactose-deficient IgA1-containing immune complexes and protects mesangial cells from injury in IgA nephropathy

Youxia Liu,Huyan Yu,Junya Jia,Hongfen Li,Fanghao Wang,Tiekun Yan

doi:10.1186/s12882-021-02657-8

Abstract

BackgroundThe addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. However, there is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN).MethodsThis study included a total of 184 IgAN patients. The sialylated IgG (SA-IgG), IgG-galactose-deficient IgA1 complex (IgG-Gd-IgA1-IC), IL-6, TNF-α, and TGF-β were detected using commercial ELISA kits. SA-IgG, non-sialylated IgG (NSA-IgG), sialylated IgG-IgA1 complex (SA-IgG-IgA1), and non-sialylated IgG-IgA1 complex (NSA-IgG-IgA1) were purified from IgAN patients and healthy controls (HCs).ResultsThe mean SA-IgG levels in plasma and B lymphocytes in IgAN patients were significantly higher than those of healthy controls. A positive correlation was found between SA-IgG levels in plasma and B lymphocytes. In vitro, the results showed that the release of IgG-Gd-IgA1-IC was significantly decreased in peripheral blood mononuclear cells (PBMCs) cultured with SA-IgG from both IgAN patients and healthy controls. The proliferation ability and the release of IL-6, TNF-α, and TGF-β in human mesangial cells (HMCs) were measured after stimulating with SA-IgG-IgA1-IC and NSA-IgG-IgA1-IC. The mesangial cell proliferation levels induced by NSA-IgG-IgA1-IC derived from IgAN patients were significantly higher than those caused by SA-IgG-IgA1-IC derived from IgAN patients and healthy controls. Compared with NSA-IgG-IgA1 from healthy controls, IgAN-NSA-IgG-IgA1 could significantly upregulate the expression of IL-6 and TNF-α in mesangial cells. The data showed that there weren’t any significant differences in the levels of IL-6, TNF-α, and TGF-β when treated with IgAN-SA-IgG-IgA1 and HC-NSA-IgG-IgA1.ConclusionsThe present study demonstrated that the sialylation of IgG increased in patients with IgA nephropathy. It exerted an inhibitory effect on the formation of Gd-IgA1-containing immune complexes in PBMCs and the proliferation and inflammation activation in mesangial cells.

Highlights

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world, with 10% of patients will progress to end-stage kidney disease within 10 years after diagnosis [1, 2]
We further explored the association of plasma SAIgG with clinical findings and pathological lesions in patients with IgA nephropathy (IgAN)
We found that patients with higher Sialylation of IgG (SA-IgG) levels (OD > 2.02) had significantly lower levels of galactose-deficient IgA1 (Gd-IgA1) compared with those patients with lower SA-IgG (OD < 2.02) (Table 1)

Summary

Introduction

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world, with 10% of patients will progress to end-stage kidney disease within 10 years after diagnosis [1, 2]. An intravenous immunoglobulin used to treat various autoimmune and inflammatory disease has an antiinflammatory effect due to IgG-Fc glycans rich in sialic acid [7, 8]. Lack of terminal sialic acids in IgG (NSA-IgG) enhances the proinflammatory activity. There is a lack of research on the changes of IgG sialylation in IgAN. The addition of sialic acid alters IgG from a pro-inflammatory state to an anti-inflammatory state. There is a lack of research on the changes of IgG sialylation in IgA nephropathy (IgAN)

Methods

Results

Discussion

Conclusion