Proosteoclastogenic state in patients with Gaucher Disease: correlation with bone pathology

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

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; 2016

Gaucherdisease is the most frequent lysosomal storage disease. This autosomicrecessive disease is caused by mutations on the gene encoding for the lysosomalenzyme glucocerebrosidase, that leads to the accumulation of its substrate, glucosylceramide. Clinical manifestations include anemia, hepatosplenomegaly and bone alterations.In spite of treatment, bone alterations in Gaucher patients persist.Chitotriosidase is the most reliable biomarker used in the follow up of thedisease, although its correlation with bone status has not been studied. The aim of our work was to study the proosteoclastogenic potential in patients andto evaluate its correlation with chitotriosidase activity levels and clinicalparameters. To evaluate the proosteoclastogenic state, PBMC from patients underEnzyme Replacement Therapy were obtained by ficoll gradient and cultured in thepresence of M-CSF. Mature osteoclasts were defined as multinucleated TRAPpositive cells. On the other hand, the bone mineral density (BMD) of the totalskeleton and lumbar spine was evaluated in patients as well as serum levels of crosslaps (CTX) and chitotriosidase. As expected, serum chitotriosidase activity washigher in patients. We also found that osteoclast differentiation was increasedin patients. However, no correlation between osteoclasts and serumchitotriosidase was observed. Osteoclast levels presented a negativecorrelation with BMD expressed as Z-score (both total skeleton and spine) whilea positive correlation with CTX was observed. In conclusion, our results showfor the first time a correlation between osteoclast differentiation and boneclinical parameters in Gaucher disease, but not with chitotriosidase. Inaddition, these results support the involvement of osteoclasts in the bonepathology of Gaucher disease.