Abstract: TH-PO100

Galactose-Deficient IgA1 Monoclonal Antibody Specifically Identifies Primary IgA Nephropathy and IgA Vasculitis with Nephritis

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Suzuki, Hitoshi, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Yasutake, Junichi, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan
  • Makita, Yuko, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Yamasaki, Kohei, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan
  • Kano, Toshiki, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
Background

Galactose-deficient IgA1 (Gd-IgA1) has been proposed as an important effecter molecule in patients with IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAV-N). Our previous study revealed that Gd-IgA1-specific monoclonal antibody KM55 (KM55 mAb) could be a new tool for detecting circulatory Gd-IgA1 in patients with IgAN, which enabled us to study molecular roles of Gd-IgA1. In this study, we further examined pathophysiological significance of Gd-IgA1 in glomerular deposits of patients with IgAN and IgAV-N by immunohistochemical analysis with KM55 mAb.

Methods

Kidney biopsy specimens were obtained from 2013 to 2016 at Juntendo University Hospital with the informed consent from patients. Double Immunofluorescent staining of Gd-IgA1 with KM55 mAb and anti-human IgA antibody was performed in paraffin embedded sections of renal biopsy specimens from patients with IgAN (n=43), and other renal diseases (n=30); such as lupus nephritis, HCV-related nephropathy and IgAV-N.

Results

Glomerular Gd-IgA1 was specifically detected by KM 55 mAb in all patients with IgAN and IgAV-N. In patients with IgAN and IgAV-N, Gd-IgA1 was localized predominantly in the mesangial region as IgA deposition. Gd-IgA1 could not be detected even in patients with lupus nephritis accompanied by glomerular IgA deposition. Furthermore, HCV-related nephropathy with secondary IgA deposition after HCV infection did not show any glomerular Gd-IgA1.

Conclusion

This is the first observation to clearly indicate that Gd-IgA1 could be specifically deposited in glomeruli of IgAN and IgAV-N, strongly suggesting the pathophysiological function of Gd-IgA1 in those diseases. Further studies are necessary to clarify the underlying mechanisms of Gd-IgA1 deposition and induction of renal injuries in IgAN and IgAV-N. Monoclonal antibody against Gd-IgA1 could be a novel powerful tool to distinguish primary IgAN and IgAV-N from other renal diseases with glomerular IgA.

Funding

  • Government Support - Non-U.S.