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Original Article
Fabry disease: characterisation of the plasma proteome pre- and post-enzyme replacement therapy


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 Two-dimensional electrophoresis and matrix-assisted 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 After 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 (ACTB), 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 These results indicated that C3-mediated complement activation might be altered in Fabry disease and ERT might promote its stabilisation.

  • Beta-actin
  • Biomarker
  • Complement
  • C3
  • Fabry disease

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  • Contributors SHH, HWY, RJD, and BHL designed the research project and SCJ, JHC, and RJD supervised the experiments. EK, YMK, and IHC reviewed the clinical findings. SHH, JMK, JMK, GHK, and LBH analysed the proteomics data. SHH, MK, KYK, and JYJ performed the in vitro studies. HG reviewed the pathological findings. SHH, GHK, HG, and BHL wrote the manuscript, which was then reviewed critically by JHC, HWY, SCJ, and RJD. All co-authors read and approved the final manuscript.

  • Funding This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Korean government (MSIP&MOHW) (NRF-2016M3A9B4915706).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The institutional review board of the Asan Medical Center, Seoul, Korea.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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