Profiles of Globotriaosylsphingosine Analogs and Globotriaosylceramide Isoforms Accumulated in Body Fluids from Various Phenotypic Fabry Patients

• Published in: Internal Medicine 2024/06/01, Vol.63(11), pp.1531-1537
• Main Authors: Shiga, Tomoko, Tsukimura, Takahiro, Kubota, Takao, Togawa, Tadayasu, Sakuraba, Hitoshi
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; alpha-Galactosidase - metabolism; Antibodies; biomarker; Biomarkers - blood; Body fluids; Body Fluids - chemistry; Body Fluids - metabolism; Enzyme Replacement Therapy; Fabry disease; Fabry Disease - blood; Fabry Disease - metabolism; Fabry's disease; Female; Globotriaosylceramide; globotriaosylceramide isoforms; globotriaosylsphingosine; globotriaosylsphingosine analogs; Glycolipids - blood; Glycolipids - metabolism; Humans; Isoforms; Liquid chromatography; Male; Mass spectroscopy; Middle Aged; Original; Phenotype; Protein Isoforms; Sphingolipids - blood; Sphingolipids - metabolism; Tandem Mass Spectrometry; Trihexosylceramides - blood; Trihexosylceramides - metabolism; Young Adult
• ISSN: 0918-2918; 1349-7235; 1349-7235
• DOI: 10.2169/internalmedicine.2493-23

Objectives Fabry disease is characterized by the systemic accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3), which are widely used as biomarkers of the disease. However, few reports have described the relationship of Lyso-Gb3 analogs and Gb3 isoforms with the disease. The present study determined the profiles of Lyso-Gb3 analogs and Gb3 isoforms accumulated in body fluids from various phenotypic Fabry patients to elucidate the basis of the disease. Methods Plasma Lyso-Gb3 and related analogs were measured in 15 classic Fabry men, 6 later-onset Fabry men, 11 Fabry women, and 36 controls, while urinary Gb3 isoforms were measured in 5 classic Fabry men, 5 later-onset Fabry men, 17 Fabry women, and 11 controls, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, these values were monitored for a classic Fabry man, in whom neutralizing anti-drug antibodies had developed following enzyme replacement therapy (ERT). Results The levels of plasma Lyso-Gb3 analogs/urinary Gb3 isoforms were higher in Fabry patients than in controls, especially in classic Fabry men. However, minor differences in the ratio of each Lyso-Gb3 analog and Gb3 isoform with respect to the total Lyso-Gb3 analogs and Gb3 isoforms, respectively, were observed among individual classic Fabry men. Their time courses were well associated with the development and attenuation of anti-drug antibodies in a patient with classic Fabry disease during ERT. Conclusion Quantification of Lyso-Gb3 analogs and Gb3 isoforms provides us with more detailed information about the substrates that accumulated in the body fluids of Fabry patients than does quantification of Lyso-Gb3 and Gb3 alone, so this approach may be useful for elucidating the basis of Fabry disease.