Shinya Ishiko1, Akihito Tanaka2, Asami Takeda2, Masayuki Hara3, Naoto Hamano4, Masahiro Koizumi4, Toshinori Ueno5, Hiroki Hayashi6, Atsushi Kondo7, Sadayuki Nagai7, Yuya Aoto7, Nana Sakakibara7, China Nagano7, Tomoko Horinouchi7, Tomohiko Yamamura7, Takeshi Ninchoji7, Yuko Shima8, Koichi Nakanishi9, Norishige Yoshikawa10, Kazumoto Iijima7, Kandai Nozu7. 1. Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. ishiko@med.kobe-u.ac.jp. 2. Department of Nephrology, Japanese Red Cross Nagoya Daini Hospital, 2-9 Myoken-cho, Showa-ku, Nagoya, Aichi, 466-8650, Japan. 3. Department of Nephrology, Omihachiman Community Medical Center, 1379 Tsuchida-cho, Omihachiman, Shiga, 523-0082, Japan. 4. Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. 5. Department of Nephrology, Hiroshima Prefectural Hospital, 1-5-54 Ujinakanda, Minami-ku, Hiroshima, Hiroshima, 734-8530, Japan. 6. Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan. 7. Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. 8. Department of Pediatrics, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, 641-8509, Japan. 9. Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa, 903-2015, Japan. 10. Clinical Research Center, Takatsuki General Hospital, 1-3-13 Kosobe-cho, Takatsuki, Osaka, 569-1192, Japan.
Abstract
BACKGROUND: Pathological findings in Alport syndrome frequently show mesangial proliferation and sometimes incidental IgA deposition, in addition to unique glomerular basement membrane (GBM) changes including thin basement membrane and/or lamellation. However, similar GBM abnormalities are also often observed in IgA nephropathy. Both diseases are also known to show hematuria, proteinuria, and sometimes macrohematuria when associated with viral infection. Therefore, it can be difficult to make a differential diagnosis, even based on clinical and pathological findings. Some recent articles demonstrated that galactose-deficient IgA1 (Gd-IgA1)-specific monoclonal antibody (KM55) could potentially enable incidental IgA deposition to be distinguished from IgA nephropathy. METHODS: We performed comprehensive gene screening and glomerular Gd-IgA1 and type IV collagen α5 chain immunostaining for five cases with both IgA deposition and GBM changes to confirm that Gd-IgA1 can help to distinguish these two diseases. RESULTS: Four of the cases were genetically diagnosed with Alport syndrome (Cases 1-4) and one was IgA nephropathy with massive GBM changes, which had a negative gene test result (Case 5). In Cases 1-4, glomerular Gd-IgA1 deposition was not detected, although there was positivity for IgA in the mesangial area. In Case 5, glomerular Gd-IgA1 deposition was observed. CONCLUSION: Gd-IgA1 expression analysis could clearly differentiate these two disorders. This approach can be applied to identify these two diseases showing identical clinical and pathological findings.
BACKGROUND: Pathological findings in Alport syndrome frequently show mesangial proliferation and sometimes incidental IgA deposition, in addition to unique glomerular basement membrane (GBM) changes including thin basement membrane and/or lamellation. However, similar GBM abnormalities are also often observed in IgA nephropathy. Both diseases are also known to show hematuria, proteinuria, and sometimes macrohematuria when associated with viral infection. Therefore, it can be difficult to make a differential diagnosis, even based on clinical and pathological findings. Some recent articles demonstrated that galactose-deficient IgA1 (Gd-IgA1)-specific monoclonal antibody (KM55) could potentially enable incidental IgA deposition to be distinguished from IgA nephropathy. METHODS: We performed comprehensive gene screening and glomerular Gd-IgA1 and type IV collagen α5 chain immunostaining for five cases with both IgA deposition and GBM changes to confirm that Gd-IgA1 can help to distinguish these two diseases. RESULTS: Four of the cases were genetically diagnosed with Alport syndrome (Cases 1-4) and one was IgA nephropathy with massive GBM changes, which had a negative gene test result (Case 5). In Cases 1-4, glomerular Gd-IgA1 deposition was not detected, although there was positivity for IgA in the mesangial area. In Case 5, glomerular Gd-IgA1 deposition was observed. CONCLUSION: Gd-IgA1 expression analysis could clearly differentiate these two disorders. This approach can be applied to identify these two diseases showing identical clinical and pathological findings.
Entities:
Keywords:
Alport syndrome; Galactose-deficient IgA1; Glomerular basement membrane; IgA nephropathy
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