Evaluation of Proinflammatory Prognostic Biomarkers for Fabry Cardiomyopathy With Enzyme Replacement Therapy.

BACKGROUND

Fabry disease (FD) causes progressive glycosphingolipid accumulation and damage in various organs, and several proinflammatory processes may be involved in this disease. Enzyme replacement therapy (ERT) can reduce the severity of Fabry cardiomyopathy (FC), but whether ERT could attenuate proinflammatory cytokines in FC remains unclear. In this study, we attempted to evaluate the efficacy of ERT on proinflammatory cytokines and vascular cell adhesion biomarkers.

METHODS

We enrolled 25 patients with FC and administered ERT to them according to the present clinical guideline. We analyzed and compared echocardiographic and blood examination results between 25 patients with FD without left ventricular hypertrophy (LVH), 25 patients with FC with LVH who were receiving ERT, and 25 healthy age- and sex-matched controls. The parameters of cardiac function at baseline and 12 months after ERT were assessed through echocardiography, and the expression profiles of proinflammatory biomarkers were determined.

RESULTS

Left ventricular mass (LVM), LVM index (LVMI), interventricular septal thickness at diastole, and serum levels of globotriaosylsphingosine (Gb3) were elevated in patients with FC. Meanwhile, several proinflammatory cytokines, including interleukin (IL)-6, IL-2, IL-1b, tumor necrosis factor-α, intercellular adhesion molecule, soluble vascular cell adhesion molecule, and monocyte chemoattractant protein-1 (MCP-1) were concomitantly increased. ERT significantly reduced these transthoracic echocardiographic parameters and lyso-Gb3 and proinflammatory cytokine levels. The changes in IL-6, MCP-1, and lyso-Gb3 levels were positively correlated with the change in LVMI.

CONCLUSIONS

Our study has revealed that proinflammatory biomarkers, particularly IL-6 and MCP-1, may represent effective biomarkers for evaluating ERT outcomes in patients with FC.