Fabry disease: Characterisation of the plasma proteome pre- and post-enzyme replacement therapy

Sun Hee Heo, Eungu Kang, Yoon Myung Kim, Heounjeong Go, Kyung Yong Kim, Jae Yong Jung, Minji Kang, Gu Hwan Kim, Jae Min Kim, In Hee Choi, Jin Ho Choi, Sung Chul Jung, Robert J. Desnick, Han Wook Yoo, Beom Hee Lee

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Background Fabry disease is characterised by the progressive accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in vascular endothelial cells. Enzyme replacement therapy (ERT) clears this accumulation. We analysed plasma proteome profiles before and after ERT to characterise its molecular pathology. Methods T wo-dimensional electrophoresis and matrixassisted laser desorption/ionisation-time of flight tandem mass spectrometry (MALDI-TOF MS) and tandem mass spectrometry (MS/MS) were done using plasma samples before and after ERT in eight patients with classical Fabry disease Results A fter short-term ERT (4-12 months), the levels of 15 plasma proteins involved in inflammation, oxidative and ischaemic injury, or complement activation were reduced significantly. Among them, β-actin (ACT B), inactivated complement C3b (iC3b), and C4B were elevated significantly in pre-ERT Fabry disease plasma compared with control plasma. After longer-term ERT (46-96 months), iC3b levels gradually decreased, whereas the levels of other proteins varied. The gradual reduction of iC3b was comparable to that of Gb3 levels. In addition, iC3b increased significantly in pre-ERT Fabry disease mouse plasma, and C3 deposits were notable in renal tissues of pre-enzyme replacement therapy patients. Conclusion T hese results indicated that C3-mediated complement activation might be altered in Fabry disease and ERT might promote its stabilisation.

Original languageEnglish
Pages (from-to)771-780
Number of pages10
JournalJournal of Medical Genetics
Issue number11
StatePublished - 1 Nov 2017

Bibliographical note

Funding Information:
The authors would like to thank all patients and families for their cooperation in this study. This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Korean government (MSIP and MOHW) (NRF-2016M3A9B4915706).

Publisher Copyright:
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017.


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