Hypereosinophilic syndromes (HES) constitute a heterogenous group of disorders, characterized by sustained hypereosinophilia associated with eosinophil-mediated organ damage and dysfunction. Recent studies have shown that distinct pathogenic mechanisms involving either myeloid stem cells (M-HES) or interleukin (IL)-5 producing T lymphocytes (L-HES) can lead to uncontrolled eosinophil expansion in patient subgroups. A recent study has shown that mepolizumab, a monoclonal anti-IL-5 antibody, is a valid therapy of the syndrome but there is concern about the use of this treatment in L-HES patients as it doesn't target the affected T cells which can undergo malignant transformation. The aims of this study are to identify biomarkers for L-HES, to facilitate the diagnosis and the monitoring of this variant, and to identify potential new targets for its treatment. Our preliminary investigations suggest that increased serum levels of the chemokine TARC (CCL17) could be specific for L-HES and we recently identified a series of immune-related receptors and signalling molecules whose transcription level is significantly modified in T cells from affected patients. We will determine whether these observations point towards novel biomarkers with increased specificity for the diagnosis of L-HES, and/or early detection of malignant transformation of T lymphocytes.

Principal investigator: Florence ROUFOSSE (MD-PhD)
Post-doctoral fellow: Issam HARFI
Technical assistants: Fatima LAMRANNI

K. WILLARD-GALLO, Bordet Institute, ULB
M. CAPRON, University Hospital of Lille, France
L. PRIN, University Hospital of Lille, France
S. RAHMOUNI, ULG, Belgium
L. DE LEVAL, ULG, Belgium

Roufosse F, Klion A, Weller P. Clinical manifestations, pathophysiology, and diagnosis of the hypereosinophilic syndromes. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2008

Roufosse F, Klion A, Weller P. Treatment of the hypereosinophilic syndromes. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2008

Ogbogu P, Bochner B, Butterfield J, Gleich G, Huss-Marp J, Kahn JE, Leiferman K, Nutman T, Pfab F, Ring J, Rothenberg M, Roufosse F, Sajous MH, Sheikh J, Simon D, Simon HU, Stein M, Wardlaw A, Weller P, Klion A. Hypereosinophilic syndromes: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Aller Clin Immunol 2009; 124: 1319-25.

Ravoet M, Sibille C, Gu C, Libin M, Haibe-Kains B, Sotiriou C, Goldman M, Roufosse F, Willard-Gallo K. Molecular profiling of CD3-CD4+ T cells from patients with the lymphocytic variant of hypereosinophilic syndrome reveals targeting of growth control pathways. Blood 2009;114: 2969-83.

Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller P, Simon HU, Schwartz L, Rosenwasser L, Ring J, Griffin E, Haig A, Frewer P, Parkin J, Gleich G. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med 2008; 358: 1215-1228

Thielen C, Radermacher V, Trimeche M, Roufosse F, Goldman M, Boniver J, de Leval L. TARC and IL-5 expression correlates with tissue eosinophilia in peripheral T-cell lymphomas. Leuk Res 2008; 32 : 1431-1438

Roufosse F, Cogan E, Goldman M. Lymphocytic variant hypereosinophilic syndromes. Immunol Aller Clin North Am 2007; 27: 389-413

Ravoet M, Sibille C, Roufosse F, Duvillier H, Sotiriou C, Schandené L, Martiat P, Goldman M, Willard-Gallo K. 6q- is an early and persistent chromosomal aberration in the CD3-CD4+ T cell clones associated with the lymphocytic variant of hypereosinophilic syndrome. Haematologica 2005; 90: 753-765

Willard-Gallo KE, Badran BM, Ravoet M, Zerghe A, Burny A, Martiat P, Goldman M, Roufosse F, Sibille C. Defective CD3g gene transcription is associated with NFATc2 overexpression in the lymphocytic variant of hypereosinophilic syndrome. Exp Hematol 2005; 33: 1147-1159

Roufosse F, Cogan E, Goldman M. Recent advances in pathogenesis and management of hypereosinophilic syndromes. Allergy 2004; 59: 673-689

Roufosse F, Cogan E, Goldman M. The idiopathic hypereosinophilic syndrome revisited. Ann Rev Med 2003; 54: 169-184

de Lavareille A, Roufosse F, Schmid-Grendelmeier P, Roumier AS, Schandené L, Cogan E, Simon HU, Goldman M. High serum thymus and activation-regulated chemokine levels in the lymphocytic variant of the hypereosinophilic syndrome. J Aller Clin Immunol 2002; 110: 476-479

Roufosse F, Schandené L, Sibille C, Willard-Gallo K, Kennes B, Efira A, Goldman M, Cogan E. Clonal Th2 lymphocytes in patients with the idiopathic hypereosinophilic syndrome. Br J Haematol 2000; 109: 540-548

Roufosse F, Schandené L, Sibille C, Kennes B, Efira A, Cogan E, Goldman M. T-cell receptor-independent activation of clonal Th2 cells associated with chronic hypereosinophilia. Blood 1999; 94: 994-1002

Government of the Walloon Region
GSK Biologicals
The Fund for Scientific Research (F.R.S - FNRS) and the Télévie Programme
The Belgian Science Policy
The European Commission
The Erasme Fund
The Wiener-Anspach Foundation
The Belgian Kid's Fund
The Roche Organ Transplantation Research Foundation
The Dimitris and Noela Nakos Foundation
Roche Pharmaceuticals, Belgium
Wittycell S.A.S