Diagnosis and activity assessment of immunoglobulin A nephropathy: current perspectives on noninvasive testing with aberrantly glycosylated immunoglobulin A-related biomarkers.
Immunoglobulin (Ig) A nephropathy (IgAN) is the most common form of glomerular disease worldwide and is associated with a poor prognosis. Thus, development of a curative treatment and strategies for early diagnosis and treatment are urgently needed. Pathological analysis of renal biopsy is the gold standard for the diagnosis and assessment of disease activity; however, immediate and frequent assessment based on biopsy specimens is difficult. Therefore, a simple and safe alternative is desirable. On the other hand, it is now widely accepted that multi-hit steps, including production of aberrantly glycosylated serum IgA1 (first hit), and IgG or IgA autoantibodies that recognize glycan containing epitopes on glycosylated serum IgA1 (second hit) and their subsequent immune complex formation (third hit) and glomerular deposition (fourth hit), are required for continued progression of IgAN. Although the prognostic and predictive values of several markers have been discussed elsewhere, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of glycosylated serum IgA1 and related IgA immune complex. In addition, we confirmed a significant correlation between serum levels of these essential effector molecules and disease activity after treatment, suggesting that each can be considered as a practical surrogate marker of therapeutic effects in this slowly progressive disease. Such a noninvasive diagnostic and activity assessment method using these disease-oriented specific biomarkers may be useful in the early diagnosis of and intervention in IgAN, with appropriate indication for treatment, and thus aid in the future development and dissemination of specific and curative treatments.
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Yusuke
Y
Suzuki
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Hitoshi
H
Suzuki
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Yuko
Y
Makita
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Akiko
A
Takahata
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Keiko
K
Takahashi
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Masahiro
M
Muto
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Yohei
Y
Sasaki
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Atikemu
A
Kelimu
Kyoto University Health Service, Kyoto, Japan.
Keiichi
K
Matsuzaki
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Hiroyuki
H
Yanagawa
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Keiko
K
Okazaki
Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo.
Yasuhiko
Y
Tomino
N-acetylgalactosamine; anti-glycan antibody; galactose-deficient immunoglobulin A1; immune complex; surrogate marker