TY - JOUR T1 - Fabry disease: characterisation of the plasma proteome pre- and post-enzyme replacement therapy JF - Journal of Medical Genetics JO - J Med Genet SP - 771 LP - 780 DO - 10.1136/jmedgenet-2017-104704 VL - 54 IS - 11 AU - Sun Hee Heo AU - Eungu Kang AU - Yoon-Myung Kim AU - Heounjeong Go AU - Kyung Yong Kim AU - Jae Yong Jung AU - Minji Kang AU - Gu-Hwan Kim AU - Jae-Min Kim AU - In-Hee Choi AU - Jin-Ho Choi AU - Sung-Chul Jung AU - Robert J Desnick AU - Han-Wook Yoo AU - Beom Hee Lee Y1 - 2017/11/01 UR - http://jmg.bmj.com/content/54/11/771.abstract N2 - 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. ER -