SERUM CYTOKINE PROFILE IN TYPE 1 GAUCHER DISEASE PATIENTS CORRELATES WITH BONE PATHOLOGY

ROZENFELD, PAULA; CECI, ROMINA; BONDAR, CONSTANZA; OLIVERI, BEATRIZ; MUCCI, JUAN MARCOS; GONZALEZ, DIANA; ORMAZABAL, MAXIMILIANO; CRIVARO, ANDREA

Congreso; Reunion conjunta de sociedades de biociencias; 2017

Gaucherdisease (GD) is caused by mutations on the gene encoding for the lysosomalenzyme glucocerebrosidase. Type I GD (GD1) patients present anemia,hepatosplenomegaly and bone alterations. In spite of treatment, bone alterationsin GD patients persist, including poor bone mineral density (BMD). Mechanismsleading to bone damage are not completely understood, but previous reportssuggest that osteoclasts are involve. It is known that bone remodeling isregulated by the immune system, in part, through cytokines like TNFα (inductorof osteoclastogenesis), TGFβ, IL-10 and INFϒ (inhibitors of osteoclastsdifferentiation). On the other hand, it has been demonstrated that theaccumulation of glucocerebrosidase in GD can induce macrophage activation andsecretion of cytokines such as Il-6, IL-1β and TNFα. The aim of this work wasto evaluate cytokines profile (TNFα, IL-6, TGFβ, IL-10 and INFϒ) and bonebiomarkers (CTX and BAP) in treated patient´s serum and evaluate its relationwith BMD and the pro-osteoclastogenic potential. The number of osteoclasts wasdetermined by cultured PBMCs with M-CSF and stained for tartrate-resistant acidphosphatase (TRAP). CTX and BAP were assessed by electrochemiluminescence andenzyme immunoassay, respectively; and cytokines were measured by ELISA. Serumlevels of CTX in adult and pediatric GD1 patients were increased (p<0,01;p<0,05, respectively) as well as BAP in adult GCD1 (p=0,05). We also observedthat pediatric group had a positive correlation with the pro- osteoclastogenicpotential (number of osteoclasts) (r=0,8338 p=0,0052). Serum cytokines werealso altered showing a pro-osteoclastogenic status and a positive correlationbetween IL-10/ INF-ϒ with BMD (express as Z-score) was observed (r= 0,5134p=0,0420; r=0,5751 p=0,0198, respectively). Our results suggest the involvementof osteoclasts in the bone pathology of GD1, and an altered immune responsewhich may play an important role in bone damage.