PRODUCTION OF PROINFLAMMATORY CYTOKINES BY MONONUCLEAR CELLS FROM FABRY DISEASE PATIENTS. ROLE OF GLOBOTRIAOSILCERAMIDE

ROZENFELD PA; DE FRANCESCO, PN; MUCCI JM; CECI, R

Congreso; Annual Symposium of SSIEM 2012; 2012

Background: Fabry disease is a lysosomal storage disorder associated to accumulation of globotriaosilceramide (Gb3). Pathological mechanisms of this disorder are poorly understood, chronic inflammation was suggested as one of the contributing factors. The aim is to analyze cytokine levels in peripheral blood mononuclear cells (PBMC) from Fabry disease patients, as well as to test the effect of Gb3 addition to normal control cells on cytokine secretion. Methods: PBMC from Fabry disease patients and normal controls were incubated with specific antibodies for surface markers (CD56, CD3, LIN1, HLA-DR, CD14) and the cytokines IL-1β, IL-6, y TNF-α (intracellular staining), and assessed by flow cytometry. Moreover monocytes and dendritic cells obtained from normal donors were incubated with Gb3 and DGJ (GLA inhibitor), and secretion of cytokines were determined in culture supernatants. Results: We found higher levels of TNF-α and IL-1β (p