FP233
Galactose-deficient IgA1 represent a candidate urinary marker of IgA nephropathy

INTRODUCTION: In patients with IgA nephropathy (IgAN), circulatory IgA1 and IgA1 in mesangial deposits contain elevated amounts of galactose-deficient IgA1 (Gd-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 135 patients with IgAN and 80 patients with other renal diseases (control) hospitalized from 2015 to 2018. Urine samples collected at the time of renal biopsy were used to measure Gd-IgA1 using KM55 mAb. Moreover, consecutive urinary Gd-IgA1 were measured during the course of therapy in 51 patients with IgAN. Next, we validated urinary Gd-IgA1 using KM55 mAb in biopsy proven 69 patients with IgAN and 38 controls in korean.

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. In Korean cohort, urinary Gd-IgA1 levels also were significantly higher in patients with IgAN compared with control (P=0.017).

CONCLUSIONS: In summary, urinary excretion of 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. Urinary Gd-IgA1 is also useful to determine disease activity. Urinary Gd-IgA1 may thus represent a disease-specific biomarker of IgAN.