Study of urinary proteomes in Anderson-Fabry disease

Anderson-Fabry disease (AFD) is an X-linked genetic disorder with deficient α-galactosidase A activity. The main aim of this work was to investigate possible differences in urine proteins between healthy controls and AFD patients and to identify abnormal proteins as potential biomarkers of disease.

We studied 2D electrophoresis images of urine samples collected from AFD patients and healthy subjects. The proteins were separated using isoelectric focusing method followed by SDS-PAGE. The proteins were then visualized by silver staining and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

We found out that the urinary spectra of all the Fabry disease samples included identical proteins with molecular weight around 20-40 kDa. The concentration of some proteins was more than three times higher in the AFD samples, compared to the controls. The abundant proteins were identified by MALDI-TOF MS and included the following: alpha-1-antitrypsin, alpha-1-microglobulin, prostaglandin H2 d-isomerase, complement-c1q tumor necrosis factor-related protein, and Ig kappa chain V-III. Possible glycosylation at Asn51 and Asn78 sites of the prostaglandin H2 d-isomerase was detected.

AFD urinary proteomics revealed increased secretion of several proteins. We postulate that the observed difference in the amount of prostaglandin H2 d-isomerase and its position on two-dimensional gels might be related to different glycosylation in AFD subjects.