PROOSTEOCLASTOGENIC STATE IN PATIENTS WITH GAUCHER DISEASE: CORRELATION WITH BONE PATHOLOGY.

BONDAR C.; CRIVARO A.; CECI R.; ORMAZABAL M.; MUCCI J.M.; ROZENFELD P.

Mar del Plata

Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2016

Gaucher disease is the most frequent of lysosomal storage diseases.This autosomic recessive disease is caused by mutations onthe gene encoding for the lysosomal enzyme glucocerebrosidase.Deficiency of this enzyme leads to the accumulation of its substrateglucosylceramide, mainly in macrophages. Clinical manifestationsinclude anemia, hepatosplenomegaly and bone alterations. In spiteof treatment, bone alterations in Gaucher patients persist. Chitotriosidaseis the most reliable biomarker used in the follow up ofthe disease, although its correlation with bone status has not beenstudied. Previous results suggest that osteoclasts are involvedin bone tissue damage during the disease. The aim of our workwas to study the pro-osteoclastogenic potential in patients andto evaluate its correlation with chitotriosidase activity levels andclinical parameters. To evaluate the pro-osteoclastogenic state,PBMC from patients under Enzyme Replacement Therapy wereobtained by ficoll gradient and cultured in the presence of M-CSF.Mature osteoclasts were defined as multinucleated TRAP positivecells. On the other hand, z-scores from bone densitometry (total and column) were analyzed in patients, as well as serum levelsof CTX and chitotriosidase. As expected, serum chitotriosidaseactivity was higher in patients. We also found that osteoclastdifferentiation was increased in patients. However, no correlationbetween osteoclasts and serum chitotriosidase was observed.Osteoclast levels presented a negative correlation with z-score(both total and column) while a positive correlation with CTXwas observed. In conclusion, our results show for the first timea correlation between osteoclast differentiation and bone clinicalparameters in Gaucher disease, but not between osteoclasts andchitotriosidase. In addition, these results support the involvementof osteoclasts in the bone pathology of Gaucher disease.