Serum cytokine profile in type 1 gaucher disease patients correlates with bone pathology

CRIVARO A; ORMAZABAL MAXIMILIANO; GONZALEZ D; MUCCI JM; OLIVERI B; BONDAR C; CECI R; ROZENFELD PA

Congreso; Reunión anual de SAI 2017; 2017

SAI

Gaucher disease (GD) is caused by mutations on the gene encoding for the lysosomal enzyme glucocerebrosidase. Type I GD (GD1) patients present anemia, hepatosplenomegaly and bone alterations. In spite of treatment, bone alterations in GD patients persist, including poor bone mineral density (BMD). Mechanisms leading to bone damage are not completely understood, but previous reports suggest that osteoclasts are involve. It is known that bone remodeling is regulated by the immune system, in part, through cytokines like TNFα (inductor of osteoclastogenesis), TGFβ, IL-10 and INFϒ (inhibitors of osteoclasts differentiation). On the other hand, it has been demonstrated that the accumulation of glucocerebrosidase in GD can induce macrophage activation and secretion of cytokines such as Il-6, IL-1β and TNFα. The aim of this work was to evaluate cytokines profile (TNFα, IL-6, TGFβ, IL-10 and INFϒ) and bone biomarkers (CTX and BAP) in treated patient´s serum and evaluate its relation with BMD and the pro-osteoclastogenic potential.The number of osteoclasts was determined by cultured PBMCs with M-CSF and stained for tartrate-resistant acid phosphatase (TRAP). CTX and BAP were assessed by electrochemiluminescence and enzyme immunoassay, respectively; and cytokines were measured by ELISA. Serum levels of CTX in adult and pediatric GD1 patients were increased (p