Table 1.

Proteomic studies in FD.

Subjects	Sample Type	Methods Used	Outcomes in FD	Reference
69 FD patients and 83 healthy subjects	plasma	electrochemi-luminescence assays	FD patients: elevation of FGF2, VEGFA, VEGFC and IL-7. Non-classical FD patients: significant correlation between IL-7 and residual enzyme activity.	[88]
66 FD patients and 10 healthy subjects	urine	LC-MS/MS	Early stage and asymptomatic FD patients: elevation of albumin, uromodulin, α1-antitrypsin, glycogen phosphorylase brain form, endothelial protein receptor 1 and intracellular adhesion molecule 1.	[89]
7 FD patients and 7 healthy controls	urine-derived cells	Label-free quantitative nLC-MS/MS	46 candidate proteins with altered expression indicating an involvement of the Coordinated Lysosomal Expression and Regulation (CLEAR).	[90]
8 classic FD patients	plasma	2D electro-phoresis and MALDI-TOF-MS and MS/MS	Short-term ERT: reduction of 15 plasma proteins involved in inflammation, oxidative and ischemic injury, or complement activation. Pre-ERT: significant elevation of plasma β-actin, inactivated complement C3b (iC3b), and C4B. Longer-term ERT: gradually decreased iC3b.	[91]
11 naïve Fabry patients, 12 permanently ERT-treated patients and 12 healthy subjects	second morning urine	free approach coupled with LC-MS/MS analysis	Up-regulation: uromodulin, prostaglandin H2 D-isomerase and prosaposin.	[92]
32 FD patients and 14 healthy subjects	plasma	MS iTRAQ followed by MRM approach	Male FD patients: specific and sensitive panel of eight proteins (22 kDa protein, afamin, 𝛼1 antichymotrypsin, apolipoprotein E, 𝛽-Ala His dipeptidase, hemoglobin 𝛼-2, isoform 1 of sex hormone-binding globulin, and peroxiredoxin 2). Female FD patients: a nine-protein marker panel; where three proteins (apolipoprotein E, hemoglobin 𝛼-2, and peroxiredoxin 2) were common to both genders.	[93]
8 FD and 6 healthy subjects	PBMC	2D electro-phoresis and MALDI-TOF-MS	Downregulated: calnexin, rho GDP dissociation inhibitor 2, rho GDP-dissociation inhibitor 1, chloride intracellular channel protein 1. Up-regulated: g-enolase, 14-3-3 protein theta, 14-3-3 protein zeta/delta, and galectin-1.	[94]
10 male pediatric FD patients	urine	QTOF-MS	Prosaposin: significantly elevated in FD in and reduced after 12 months of ERT. GM2AP: elevated in the pretreatment Fabry patients and reduced after 12 months of ERT.	[95]
35 treatment-naïve female FD patients, 89 healthy subjects	urine	CE-MS	Urinary biomarker profile for female patients: diagnostics of the FD, monitoring of ERT.	[96]
20 FD patients, 10 healthy controls	urine	SDS-PAGE and MALDI-TOF MS	Differentially expressed proteins: α-1-antitrypsin, α-1-microglobulin, prostaglandin H2 D-isomerase, complement-c1q tumor necrosis factor-related protein, and Ig kappa chain V–III.	[97]
13 pediatric FD patients	serum	LC-MS/MS	Reduced after 6 months of ERT: α2-HS glycoprotein, vitamin D-binding protein, transferrin, Ig- α-2 C chain, and α-2-antiplasmin.	[98]

nLC-MS/MS, nano liquid chromatography couple to tandem mass spectrometry; MALDI-TOF-MS, matrix-assisted laser desorption/ionisation-time of flight tandem mass spectrometry; MS/MS, tandem mass spectrometry; MS-iTRAQ, mass spectrometry isobaric tags for relative and absolute quantification; MRM, multiple reaction monitoring, QTOF-MS, quadrupole time-of flight-coupled to mass spectrometry; CE-MS, capillary electrophoresis coupled to mass spectrometry; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis.