Hitoshi Sakuraba1, Tadayasu Togawa2, Takahiro Tsukimura2, Hiroshi Kato3. 1. Department of Clinical Genetics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan. sakuraba@my-pharm.ac.jp. 2. Department of Functional Bioanalysis, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan. 3. Specialty Medical Affairs Group, Medical Affairs, Sumitomo Dainippon Pharma Co., Ltd., 17-10, Kyobashi 1-Chome, Chuo-ku, Tokyo, 104-0031, Japan.
Abstract
BACKGROUND: Recently, globotriaosylsphingosine (lyso-Gb3) has attracted interest as a biomarker of Fabry disease. However, little is known regarding its utility for the evaluation of the therapeutic efficacy. METHOD: We measured plasma lyso-Gb3 concentration in Japanese healthy subjects and Fabry patients by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS). We determined the reference interval in Japanese (UMIN000016854), and examined the effect of enzyme replacement therapy (ERT) with recombinant α-galactosidase A (GLA) and the influence of antibodies against the enzyme on the plasma lyso-Gb3 level in Fabry patients (UMIN000017152). RESULTS: The reference interval was determined to be 0.35-0.71 nmol/L, this being almost the same as the normal range in a non-Japanese population previously reported. The analysis revealed that the plasma lyso-Gb3 level was strikingly increased in classic Fabry males, and to a lesser extent in later-onset Fabry males and Fabry females. The elevation of the plasma lyso-Gb3 level was related to renal involvement in the Fabry females. ERT gave a rapid reduction in the elevated plasma lyso-Gb3 level in the classic Fabry males, and a gradual one or stabilization in most of the later-onset Fabry males and Fabry females. However, formation of antibodies against the recombinant GLA had a negative effect on the reduction of plasma lyso-Gb3. CONCLUSIONS: Regular observation of plasma lyso-Gb3 and antibodies is useful for monitoring of Fabry patients during ERT.
BACKGROUND: Recently, globotriaosylsphingosine (lyso-Gb3) has attracted interest as a biomarker of Fabry disease. However, little is known regarding its utility for the evaluation of the therapeutic efficacy. METHOD: We measured plasma lyso-Gb3 concentration in Japanese healthy subjects and Fabry patients by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS). We determined the reference interval in Japanese (UMIN000016854), and examined the effect of enzyme replacement therapy (ERT) with recombinant α-galactosidase A (GLA) and the influence of antibodies against the enzyme on the plasma lyso-Gb3 level in Fabry patients (UMIN000017152). RESULTS: The reference interval was determined to be 0.35-0.71 nmol/L, this being almost the same as the normal range in a non-Japanese population previously reported. The analysis revealed that the plasma lyso-Gb3 level was strikingly increased in classic Fabry males, and to a lesser extent in later-onset Fabry males and Fabry females. The elevation of the plasma lyso-Gb3 level was related to renal involvement in the Fabry females. ERT gave a rapid reduction in the elevated plasma lyso-Gb3 level in the classic Fabry males, and a gradual one or stabilization in most of the later-onset Fabry males and Fabry females. However, formation of antibodies against the recombinant GLA had a negative effect on the reduction of plasma lyso-Gb3. CONCLUSIONS: Regular observation of plasma lyso-Gb3 and antibodies is useful for monitoring of Fabry patients during ERT.
Authors: S M Rombach; N Dekker; M G Bouwman; G E Linthorst; A H Zwinderman; F A Wijburg; S Kuiper; M A Vd Bergh Weerman; J E M Groener; B J Poorthuis; C E M Hollak; J M F G Aerts Journal: Biochim Biophys Acta Date: 2010-05-13
Authors: Henrik Gold; Mina Mirzaian; Nick Dekker; Maria Joao Ferraz; Johan Lugtenburg; Jeroen D C Codée; Gijs A van der Marel; Herman S Overkleeft; Gabor E Linthorst; Johanna E M Groener; Johannes M Aerts; Ben J H M Poorthuis Journal: Clin Chem Date: 2012-12-12 Impact factor: 8.327
Authors: Mariëlle J van Breemen; Saskia M Rombach; Nick Dekker; Ben J Poorthuis; Gabor E Linthorst; Aeilko H Zwinderman; Frank Breunig; Christoph Wanner; Johannes M Aerts; Carla E Hollak Journal: Biochim Biophys Acta Date: 2010-09-17
Authors: Johannes M Aerts; Johanna E Groener; Sijmen Kuiper; Wilma E Donker-Koopman; Anneke Strijland; Roelof Ottenhoff; Cindy van Roomen; Mina Mirzaian; Frits A Wijburg; Gabor E Linthorst; Anouk C Vedder; Saskia M Rombach; Josanne Cox-Brinkman; Pentti Somerharju; Rolf G Boot; Carla E Hollak; Roscoe O Brady; Ben J Poorthuis Journal: Proc Natl Acad Sci U S A Date: 2008-02-19 Impact factor: 11.205
Authors: Saskia M Rombach; Johannes M F G Aerts; Ben J H M Poorthuis; Johanna E M Groener; Wilma Donker-Koopman; Erik Hendriks; Mina Mirzaian; Sijmen Kuiper; Frits A Wijburg; Carla E M Hollak; Gabor E Linthorst Journal: PLoS One Date: 2012-10-19 Impact factor: 3.240
Authors: Álvaro Arbeláez-Cortés; Diana C Quintero-González; Yesid Cuesta-Astroz; Juan S Villadiego; Herman González-Buriticá; Jorge M Rueda Journal: Rheumatol Int Date: 2019-10-10 Impact factor: 2.631
Authors: Cassiano Augusto Braga Silva; Luis Gustavo Modelli de Andrade; Maria Helena Vaisbich; Fellype de Carvalho Barreto Journal: J Bras Nefrol Date: 2022 Apr-Jun
Authors: Aizeddin A Mhanni; Christiane Auray-Blais; Michel Boutin; Alie Johnston; Kaye LeMoine; Jill Patterson; Johannes M F G Aerts; Michael L West; Cheryl Rockman-Greenberg Journal: Mol Genet Metab Rep Date: 2020-06-24