Fabry disease (FD) is an X-linked inborn error caused by mutations of alfa-galactosidase A gene (GLA); the deficiency/absence of alfa-Gal A activity results in the systemic accumulation of globotriaosylceramide and related glycosphingolipids within the lysosomes in microvascular endothelial cells, vascular smooth muscle cells, renal tubular cells, podocytes and cardiomyocytes, fovouring renal failure, cardio-cerebrovascular disease and premature demise. Cardiac involvement causing FD Cardiomyopathy (FDCM) is frequent in FD.
Treatment of FB is actually based on the administration of enzyme replacement therapy (ERT) and/or the use of chaperone therapy. Early ERT administration, particularly in the pre-hypertrophic FDCM, prevents progression of the disease. Mechanisms of resistance to ERT are still unclear although expansion of interstitial space as well as myocardial fibrosis appear to be implicated. Myocardial inflammation has been indicated as potentially contributive to myocardial fibrosis and interstitial expansion. Immune-mediated myocarditis has been histologically recognized in FDCM, suggesting mechanisms inducing the interstitial release of the highly in immunogenic globotrioacylceramide (Gb3) in pts with suitable HLA characteristic an autoimmune response.
These observations forward the need of a sensitive and specific serologic biomarker of myocardial inflammation in order to halt, through administration of low dose of immunosuppression, its deleterious effect on disease progression and ERT resistance.
The aim of the study is the serum assessment of anti-Gb3 antibody as biomarker of coexistent myocardial inflammation in pts with FDCM. Its level will be compared with that of normal controls and patients with various cardiomyopathies including idiopathic dilated and hypertrofic cardiomyophy. Finally anti-Gb3 antibody titre will be correlated with severity of MI (number of CD45Ro+ T lymphocytes/2mm tissue section), in order to establish its sensitivity.
