Abstract: TH-PO822

Urinary Galactose-Deficient IgA1 Represent a Disease-Specific Marker of IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Suzuki, Hitoshi, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Kano, Toshiki, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Makita, Yuko, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Fukao, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
Background

IgA nephropathy (IgAN) is an autoimmune disease characterized by IgA1-containing immune deposits in mesangium. Galactose-deficient IgA1 (Gd-IgA1) is recognized by anti-glycan autoantibodies, resulting in formation of pathogenic immune complexes. These immune complexes deposit in the kidney, activate mesangial cells, and induce glomerular injury. We recently elucidated that glomerular Gd-IgA1 was specifically detected in IgAN, but not in the other renal diseases by immunohistochemistry using Gd-IgA1 monoclonal antibody (KM55 mAb). We hypothesized that a fraction of Gd-IgA1 from the glomerular deposits may be excreted into the urine and thus represent a disease-specific marker.

Methods

We recruited biopsy proven 129 patients with IgAN and 79 patients with other renal diseases (control) hospitalized from 2015 to 2017. Serum and urine samples collected at the time of renal biopsy were used to measure Gd-IgA1. Serum and urinary Gd-IgA1 were determined by KM55 mAb. Moreover, consecutive urinary Gd-IgA1 were measured during the course of therapy in 51 patients with IgAN.

Results

Urinary Gd-IgA1 levels were significantly higher in patients with IgAN compared with control (P<0.01). Even in patients with IgAN revealed trace proteinuria (less than 0.3g/gCr), urinary Gd-IgA1 were definitely detected. Moreover, urinary Gd-IgA1 decreased response to therapy (P<0.001). Urinary Gd-IgA1 levels were well correlated with proteinuria in patients with IgAN (P<0.001), but not in control.

Conclusion

Urinary Gd-IgA1 was elevated in patients with IgAN. The fraction of Gd-IgA1 from the glomerular deposits may be excreted into the urine, as serum levels of Gd-IgA1 did not correlate with urinary Gd-IgA1. Importantly, urinary Gd-IgA1 may be an early biomarker compared with proteinuria in patients with IgAN. U rinary Gd-IgA1 is also useful to determine disease activity. Urinary Gd-IgA1 may thus represent a disease-specific biomarker of IgAN.

Funding

  • Government Support - Non-U.S.