Grants Awarded

Principal Investigator
Julien Haroche MD, PhD
Hôpitaux de Paris, and Université – Paris, France

Date of Award
November 2009

Amount of Award
$50,000

Layperson Summary
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis first described in 1930. By now, approximately 350 cases have been reported in the world literature. ECD is a multi-organ disease characterized by heterogeneous clinical manifestations. Diagnosis is based on clinical, radiological and typical pathological features. There is an ongoing debate regarding the origin of the infiltrating histiocytes in ECD. Several cases of patients with overlapping Langerhans cell histiocytosis (LCH) and ECD have been reported in the literature, suggesting that there may be a link between these entities. Although interferon alpha is considered as a first-line therapeutic option on a long-term basis in ECD, numerous cases fail to answer this treatment in particular when central nervous and cardiovascular systems are involved, requiring more aggressive or non-validated alternative regimens. These problems underline the need for an improved understanding of the etiology and pathogenesis of ECD, which remain largely unknown.

We intend to perform a transcriptome analysis on a large international series of ECD patients (estimated 15 to 20% of the known world population of patients) in order to better understand the pathophysiology of this orphan disease. This study will draw new insights on the pathogenesis of the disease by identifying genes differentially expressed between patients and controls. This will allow better understanding of the pathways and cellular targets involved in the pathogenesis of ECD, and thus may lead to original new therapeutic options. This study has been designed as an international collaboration between French, Italian and US teams. The transcriptome analysis will be conducted in the laboratory of cellular immunology of the Hôpital Pitié-Salpêtrière, Paris, France.