PROINFLAMMATORY AND PROOSTEOCLASTOGENIC STATE IN PATIENTS WITH GAUCHER DISEASE

MUCCI JUAN M.; DELPINO M. VICTORIA; ROZENFELD PAULA

Congreso; LIX REUNIÓN CIENTÍFICA ANUAL Sociedad Argentina de Investigación Clínica LXII REUNIÓN ANUAL Sociedad Argentina de Inmunología; 2014

The aim of our work was to evaluate the proinflammatory andproosteoclastogenic environment in circulation of Patients with Gaucherdisease. The study was performed using PBMC from patientsunder ERT. The percentage of two different monocyte subsets andthe production of proinflammatory cytokines were evaluated byflow cytometry. To evaluate the proosteoclastogenic state PBMCfrom patients were cultured in the presence of M-CSF and RANKLand osteoclast differentiation and activity were assayed. Theseexperiments were carried out in the presence of Velagluceraseto study the effect of ERT. To evaluate the presence of secretedmolecules that induced osteoclast differentiation conditioned media(CM) prepared from patients PBMC was used in osteoclastogenesisinduction assays and the involvement of TNF-a and RANKL wasevaluated using neutralizing molecules. The percentage of theproinflammatory CD14+CD16+ monocyte subset was statisticallyhigher on patients (p<0.001) and an increased production of proinflammatorycytokines was observed for T cells and monocytes inpatients. Osteoclastogenesis was higher in patients (p<0.01) and invitro Velaglucerase treatment reduced osteoclast levels and activityto control levels. The induction of osteoclast differentiation by CMwas higher by patient?s CM compared to healthy controls (p<0,001)and this effect partially involved TNF-a and RANKL. In conclusionwe have shown a potential involvement of two monocyte subsets inthe proinflammatory state present in patients with Gaucher disease.PBMC from patients showed higher osteoclastogenesis which is reducedby in vitro Velaglucerase treatment. TNF-a and RANKL wouldbe involved in the potential proosteoclastogenic state in patients.