RT Journal Article
SR Electronic
T1 Fabry disease: characterisation of the plasma proteome pre- and post-enzyme replacement therapy
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 771
OP 780
DO 10.1136/jmedgenet-2017-104704
VO 54
IS 11
A1 Sun Hee Heo
A1 Eungu Kang
A1 Yoon-Myung Kim
A1 Heounjeong Go
A1 Kyung Yong Kim
A1 Jae Yong Jung
A1 Minji Kang
A1 Gu-Hwan Kim
A1 Jae-Min Kim
A1 In-Hee Choi
A1 Jin-Ho Choi
A1 Sung-Chul Jung
A1 Robert J Desnick
A1 Han-Wook Yoo
A1 Beom Hee Lee
YR 2017
UL http://jmg.bmj.com/content/54/11/771.abstract
AB 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 diseaseResults 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.