Galactose-Deficient IgA1 as a Candidate Urinary Marker of IgA Nephropathy

Yusuke Fukao; Hitoshi Suzuki; Jin Sug Kim; Kyung Hwan Jeong; Yuko Makita; Toshiki Kano; Yoshihito Nihei; Maiko Nakayama; Mingfeng Lee; Rina Kato; Jer-Ming Chang; Sang Ho Lee; Yusuke Suzuki

doi:10.3390/jcm11113173

Galactose-Deficient IgA1 as a Candidate Urinary Marker of IgA Nephropathy

J Clin Med. 2022 Jun 2;11(11):3173. doi: 10.3390/jcm11113173.

Authors

Affiliations

¹ Department of Nephrology, Faculty of Medicine, Juntendo University, Tokyo 113-8421, Japan.
² Department of Nephrology, Juntendo University Urayasu Hospital, Chiba 279-0021, Japan.
³ Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 130-701, Korea.
⁴ Division of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.

Abstract

In patients with IgA nephropathy (IgAN), circulatory IgA1 and IgA1 in the mesangial deposits contain galactose-deficient IgA1 (Gd-IgA1). Some of the Gd-IgA1 from the glomerular deposits is excreted in the urine and thus urinary Gd-IgA1 may represent a disease-specific marker. We recruited 338 Japanese biopsy-proven IgAN patients and 120 patients with other renal diseases (disease controls). Urine samples collected at the time of renal biopsy were used to measure Gd-IgA1 levels using a specific monoclonal antibody (KM55 mAb). Urinary Gd-IgA1 levels were significantly higher in patients with IgAN than in disease controls. Moreover, urinary Gd-IgA1 was significantly correlated with the severity of the histopathological parameters in IgAN patients. Next, we validated the use of urinary Gd-IgA1 levels in the other Asian cohorts. In the Korean cohort, urinary Gd-IgA1 levels were also higher in patients with IgAN than in disease controls. Even in Japanese patients with IgAN and trace proteinuria (less than 0.3 g/gCr), urinary Gd-IgA1 was detected. Thus, urinary Gd-IgA1 may be an early disease-specific biomarker useful for determining the disease activity of IgAN.

Keywords: IgA nephropathy; KM55; urinary galactose-deficient IgA1.

Grants and funding

This study was supported, in part, by the JSPS KAKENHI, Grant Numbers 15K09274 and 18K08252, and the Practical Research Project for Renal Diseases from the Japan Agency for Medical Research and Development, AMED.