Grants Awarded

Principal Investigator
Janos Sumegi MD DSc PhD
Cincinnati Children’s Hospital Medical Center – Cincinnati, Ohio USA

Date of Award
December 2010

Amount of Award
$47,500

Layperson Summary
Familial Hemophagocytic Lymphohistiocytosis (HLH) is almost universally fatal unless aggressively treated soon after diagnosis, and corrected with allogeneic bone marrow transplantation. All forms of familial HLH likely result from genetic defects in the natural down-regulating mechanisms of immune/inflammatory responses secondary to an impaired cytotoxicity by NK cells and CTLs. HLH results when critical regulatory pathways responsible for the natural termination of immune/inflammatory responses are disrupted or overwhelmed. In HLH, pathologic genetic defects alter normal crosstalk between innate and adaptive immune responses in a manner that compromises homeostatic removal of cells that are superfluous or dangerous to the organism. The purpose of this study is to compare gene expression profiles in peripheral blood mononuclear cells and subsets from patients with active, untreated HLH in order to define and better understand the pathomechanism of the disease.

Twelve Month Report

Publications
Gene Expression Profiling of Peripheral Blood Mononuclear Cells from Children with Active Hemophagocytic Lymphohistiocytosis.
Sumegi J, Barnes MG, Nestheide SV, Molleran-Lee S, Villanueva J, Zhang K, Risma KA, Grom AA, Filipovich AH.
Blood. 2011 Apr 14;117(15):e151-60. Epub 2011 Feb 16.

Gene Expression Signatures Differ Between Different Clinical Forms Of Familial Hemophagocytic Lymphohistiocytosis
Sumegi J, Nestheide SV, Barnes MG, Villanueva J, Zhang K, Grom AA, Filipovich AH.
Blood. 2013 Feb 14;121(7):e14-24. doi: 10.1182/blood-2012-05-425769. Epub 2012 Dec 20.