Clinical Significance of Galactose-Deficient IgA1 by KM55 in Patients with IgA Nephropathy

Abstract

Background: Aberrant galactose-deficient IgA1 molecules (Gd-IgA1) are important causal factors in IgA nephropathy (IgAN); however, the detection of Gd-IgA1 in IgAN is complicated and instable. A monoclonal antibody, KM55, which specifically recognizes Gd-IgA1 has been developed. In the present study, we further explored the clinical significance of Gd-IgA1 using KM55. Methods: In this study, we enrolled 75 patients with IgAN and 80 healthy controls and detected the plasma Gd-IgA1 levels using the KM55 ELISA method. We also stained ­mesangial Gd-IgA1 deposition using KM55. Results: We observed that the levels of plasma Gd-IgA1 in IgAN patients were elevated compared to the corresponding levels of healthy controls. Patients were divided into 2 groups based on the median of Gd-IgA1. Patients with high Gd-IgA1 levels had significantly higher levels of uric acid (UA) and IgA. The other clinical manifestations demonstrated that there were no differences in age, sex, blood pressure, initial proteinuria, hematuria, estimated glomerular filtration rate and Oxford pathological classification between the 2 groups of patients. In addition, positive correlations were observed between Gd-IgA1 and Bb, C3a, C4d and MAC. Mesangial Gd-IgA1 was positive in IgAN but negative in the normal renal tissue adjacent to neoplasm. We next analyzed the correlation between plasma Gd-IgA1 and mesangial Gd-IgA1 deposition. The results showed that a high level of plasma Gd-IgA1 was related to the deposition of mesangial Gd-IgA1, although the difference was not significant. Conclusion: We verified the elevated level of plasma and ­mesangial Gd-IgA1 in patients with IgAN by KM55, which provided an alternative, easy, and reliable tool for diagnosis and activity assessment of IgAN. The level of plasma Gd-IgA1 positively correlated with levels of UA, total IgA levels, and complement activation products.

Glomerular galactose-deficient IgA1 expression analysis in pediatric patients with glomerular diseases

“…The current results regarding pediatric patients with IgAN and IgAV-N are consistent with previous reports involving adult patients 7 – 10 . The anti-Gd-IgA1 monoclonal antibody KM55 was produced to detect serum Gd-IgA1 and glomerular Gd-IgA deposition in renal biopsy specimens using a novel ELISA approach.…”

“…In contrast, no Gd-IgA1 deposits were observed in any patients with non-immune related glomerulonephritis accompanied by incidental glomerular IgA deposits. The current results regarding pediatric patients with IgAN and IgAV-N are consistent with previous reports involving adult patients [7][8][9][10] . The anti-Gd-IgA1 monoclonal antibody KM55 was produced to detect serum Gd-IgA1 and glomerular Gd-IgA deposition in renal biopsy specimens using a novel ELISA approach.…”

Association Between Galactose-Deficient IgA1 Derived From the Tonsils and Recurrence of IgA Nephropathy in Patients Who Underwent Kidney Transplantation

“…The average serum Gd-IgA1 levels at the time of kidney transplantation was 5.7 μg/ml. Some reports presented serum Gd-IgA1 levels were 7.2 ± 4.0 μg/ml in healthy controls and 16.2 ± 9.1 μg/ml in native IgAN patients ( 19 , 20 ). Based on these data, serum Gd-IgA1 levels in kidney transplantation might be suppressed by immunosuppression.…”

The Complement C3a and C3a Receptor Pathway in Kidney Diseases

“…They also detected a decrease in TNF-α, TGF-β, IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1) in mouse kidneys (39). In 2019, Zhang et al found that plasma C3a in patients with IgAN was positively correlated with plasma and mesangial galactose-deficient IgA1 molecules (Gd-IgA1) (38,40).…”