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Florence Roufosse - One of the best experts on this subject based on the ideXlab platform.
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Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes.
Journal of Allergy and Clinical Immunology, 2012Co-Authors: Peter Valent, Peter F. Weller, Florence Roufosse, Amy D Klion, Hans-peter Horny, Jason Gotlib, Andrzej Hellmann, Georgia Metzgeroth, Kristin M Leiferman, Michel ArockAbstract:Eosinophilia is an important indicator of various neoplastic and nonneoplastic conditions. Depending on the underlying disease and mechanisms, eosinophil infiltration can lead to organ dysfunction, clinical symptoms, or both. During the past 2 decades, several different classifications of eosinophilic disorders and related syndromes have been proposed in various fields of medicine. Although criteria and definitions are, in part, overlapping, no global consensus has been presented to date. The Year 2011 Working Conference on Eosinophil Disorders and Syndromes was organized to update and refine the criteria and definitions for eosinophilic disorders and to merge prior classifications in a contemporary multidisciplinary schema. A panel of experts from the fields of immunology, allergy, hematology, and pathology contributed to this project. The expert group agreed on unifying terminologies and criteria and a classification that delineates various forms of Hypereosinophilia, including primary and secondary variants based on specific hematologic and immunologic conditions, and various forms of the hypereosinophilic syndrome. For patients in whom no underlying disease or hypereosinophilic syndrome is found, the term Hypereosinophilia of undetermined significance is introduced. The proposed novel criteria, definitions, and terminologies should assist in daily practice, as well as in the preparation and conduct of clinical trials.
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hypereosinophilic syndrome variants diagnostic and therapeutic considerations
Haematologica, 2009Co-Authors: Florence RoufosseAbstract:Hypereosinophilic syndromes are a group of disorders characterized by persistent and marked Hypereosinophilia not due to an underlying disease known to cause eosinophil expansion, and which is directly implicated in damage or dysfunction of at least one target organ or tissue. In this perspective article, Dr. Roufosse provides an updated classification of these disorders and discusses the recent advances in this field, including fascinating pathogenic mechanisms and novel targeted therapeutic approaches. See related paper on page 1236.
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Hypereosinophilic syndrome: lymphoproliferative and myeloproliferative variants.
Seminars in respiratory and critical care medicine, 2006Co-Authors: Florence Roufosse, Michel Goldman, Elie CoganAbstract:Idiopathic hypereosinophilic syndrome is a largely heterogeneous disorder defined as persistent, marked Hypereosinophilia of unknown origin complicated by end-organ damage. Recent research in cellular and molecular biology has led to the characterization of distinct underlying hematological disorders, primitively involving cells of the myeloid or lymphoid lineage. The ability to classify many hypereosinophilic syndrome patients on the basis of pathogenesis of Hypereosinophilia has radically changed therapeutic perspectives. Indeed, imatinib mesylate has become first-line therapy for patients in whom the FIP1L1-PDGFRalpha fusion gene is detected, whereas corticosteroids remain the mainstay for management of patients in whom Hypereosinophilia is secondary to the overproduction of interleukin 5 by abnormal T-cells. Use of monoclonal anti-interleukin-5 antibodies in the latter group of patients has a strong rationale and could decrease cumulative corticosteroid doses and toxicity. As far as prognosis of these disease variants is concerned, hypereosinophilic syndrome patients with the FIP1L1-PDGFRalpha fusion gene may develop acute myelogenous (eosinophilic) leukemia, whereas those with clonal interleukin-5-producing T-cells have an increased risk of developing T-cell lymphoma. It is currently unclear whether timely therapeutic intervention in such patients could interfere with long-term progression toward malignant hematological disorders.
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Hypereosinophilia with abnormal t cells trisomy 7 and elevated tarc serum level
Haematologica, 2003Co-Authors: A S Roumier, Florence Roufosse, Nathalie Grardel, J L Lai, I Becqueriaux, Kamel Ghomari, A De Lavareille, L Prin, M CapronAbstract:The idiopathic hypereosinophilic syndrome (HES) is a rare heterogeneous disorder, characterized by persistent blood eosinophilia with possible organ involvement. We describe here the case of a 20-year-old atopic male presenting chronic Hypereosinophilia and eczema since childhood. Biological findings included Hypereosinophilia (9.5 x 10(9)/L), hyperlymphocytosis (10.9 x 10(9)/L), polyclonal hypergammaglobulinemia and elevated IgE serum level. Flow cytometric analysis of blood lymphoid cells showed a population of CD2+CD3-CD4+TCRab-TCRgd- lymphocytes. These cells displayed a Th0/Th2 cytokine profile, and a clonal TCR rearrangement pattern. A high serum TARC level was observed. Karyotype studies on blood stimulated culture or lymph nodes revealed a cellular hyperdiploid clone 47, XY, +7. To our knowledge, this chromosomal aberration has never been reported in such case.
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clonal th2 cells associated with chronic Hypereosinophilia tarc induced ccr4 down regulation in vivo
European Journal of Immunology, 2001Co-Authors: Aurore De Lavareille, Florence Roufosse, Elie Cogan, Liliane Schandene, Patrick Stordeur, Michel GoldmanAbstract:We analyzed the expression of chemokine receptors on clonal Th2-type CD4(+)CD3(- )lymphocytes isolated from blood of two patients with chronic Hypereosinophilia. First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4 appeared following culture in human serum-free medium, suggesting that it was down-regulated in vivo. Indeed, patient's serum, but not control human serum, strongly down-regulated CCR4 expression on cultured Th2 cells. As high levels of TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic patients with CD3(-)CD4(+) clonal Th2 cells, we evaluated the effect of TARC neutralization in this system. Addition of a neutralizing anti-TARC mAb inhibited CCR4 down-regulation by patient's serum, indicating that circulating TARC contributed to CCR4 down-regulation on Th2 cells in vivo. Clonal Th2 cells did not secrete high levels of TARC themselves but induced a sustained production of TARC by monocyte-derived dendritic cells, a phenomenon that was inhibited by addition of blocking mAb against IL-4 receptor. We conclude that high circulating levels of TARC in serum of patients with chronic Hypereosinophilia, most likely derived from antigen-presenting cells stimulated by Th2-type cytokines, induce down-regulation of CCR4 on Th2 cells in vivo.
Elie Cogan - One of the best experts on this subject based on the ideXlab platform.
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Hypereosinophilic syndrome: lymphoproliferative and myeloproliferative variants.
Seminars in respiratory and critical care medicine, 2006Co-Authors: Florence Roufosse, Michel Goldman, Elie CoganAbstract:Idiopathic hypereosinophilic syndrome is a largely heterogeneous disorder defined as persistent, marked Hypereosinophilia of unknown origin complicated by end-organ damage. Recent research in cellular and molecular biology has led to the characterization of distinct underlying hematological disorders, primitively involving cells of the myeloid or lymphoid lineage. The ability to classify many hypereosinophilic syndrome patients on the basis of pathogenesis of Hypereosinophilia has radically changed therapeutic perspectives. Indeed, imatinib mesylate has become first-line therapy for patients in whom the FIP1L1-PDGFRalpha fusion gene is detected, whereas corticosteroids remain the mainstay for management of patients in whom Hypereosinophilia is secondary to the overproduction of interleukin 5 by abnormal T-cells. Use of monoclonal anti-interleukin-5 antibodies in the latter group of patients has a strong rationale and could decrease cumulative corticosteroid doses and toxicity. As far as prognosis of these disease variants is concerned, hypereosinophilic syndrome patients with the FIP1L1-PDGFRalpha fusion gene may develop acute myelogenous (eosinophilic) leukemia, whereas those with clonal interleukin-5-producing T-cells have an increased risk of developing T-cell lymphoma. It is currently unclear whether timely therapeutic intervention in such patients could interfere with long-term progression toward malignant hematological disorders.
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clonal th2 cells associated with chronic Hypereosinophilia tarc induced ccr4 down regulation in vivo
European Journal of Immunology, 2001Co-Authors: Aurore De Lavareille, Florence Roufosse, Elie Cogan, Liliane Schandene, Patrick Stordeur, Michel GoldmanAbstract:We analyzed the expression of chemokine receptors on clonal Th2-type CD4(+)CD3(- )lymphocytes isolated from blood of two patients with chronic Hypereosinophilia. First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4 appeared following culture in human serum-free medium, suggesting that it was down-regulated in vivo. Indeed, patient's serum, but not control human serum, strongly down-regulated CCR4 expression on cultured Th2 cells. As high levels of TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic patients with CD3(-)CD4(+) clonal Th2 cells, we evaluated the effect of TARC neutralization in this system. Addition of a neutralizing anti-TARC mAb inhibited CCR4 down-regulation by patient's serum, indicating that circulating TARC contributed to CCR4 down-regulation on Th2 cells in vivo. Clonal Th2 cells did not secrete high levels of TARC themselves but induced a sustained production of TARC by monocyte-derived dendritic cells, a phenomenon that was inhibited by addition of blocking mAb against IL-4 receptor. We conclude that high circulating levels of TARC in serum of patients with chronic Hypereosinophilia, most likely derived from antigen-presenting cells stimulated by Th2-type cytokines, induce down-regulation of CCR4 on Th2 cells in vivo.
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interferon α prevents spontaneous apoptosis of clonal th2 cells associated with chronic Hypereosinophilia
Blood, 2000Co-Authors: Liliane Schandene, Florence Roufosse, Elie Cogan, Aurore De Lavareille, Patrick Stordeur, Andre Efira, B Kennes, Michel GoldmanAbstract:A recent study identified a clonal expansion of CD3(-)CD4(+)cells secreting Th2-type cytokines in 4 patients with chronic Hypereosinophilia. Because interferon alpha (IFN-alpha) is used in the therapy of the idiopathic hypereosinophilic syndrome, the effects of this cytokine on the survival of clonal Th2 cells isolated from the blood of 2 patients were determined. First, these cells displayed a high rate of spontaneous apoptosis on culture in cytokine-free medium and were also sensitive to Fas-mediated apoptosis induced by soluble Fas ligand. Addition of IFN-alpha or interleukin-2 (IL-2) to culture medium resulted in significant protection against spontaneous but not Fas-induced apoptosis. Although spontaneous apoptosis of the clonal Th2 cells was clearly associated with down-regulation of both bcl-2 and bcl-x(L) levels, IFN-alpha had no significant effect on the expression of these antiapoptotic proteins, whereas addition of IL-2 resulted in higher levels of bcl-2. On the other hand, IFN-alpha decreased the numbers of cells with disrupted mitochondrial transmembrane potential both during spontaneous apoptosis and after exposure to protoporphyrin IX. Thus, IFN-alpha might promote the survival of clonal Th2 cells, an effect that could be relevant to the therapeutic approach for patients with chronic Hypereosinophilia caused by clonal expansion of Th2-type cells. (Blood. 2000;96:4285-4292)
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clonal th2 lymphocytes in patients with the idiopathic hypereosinophilic syndrome
British Journal of Haematology, 2000Co-Authors: Florence Roufosse, Michel Goldman, Liliane Schandene, Andre Efira, B Kennes, Catherine Sibille, Karen Willardgallo, Elie CoganAbstract:Idiopathic hypereosinophilic syndrome (HES) and Gleich's syndrome are related disorders characterized by persistent or recurrent Hypereosinophilia of unknown origin. Elevated IgE levels and polyclonal hypergammaglobulinaemia are considered as markers of benign outcome in this setting as they are generally associated with predominant cutaneous manifestations and favourable response to glucocorticoid therapy. In a previous study, we identified a clonal population of CD3-CD4+ Th2-like lymphocytes secreting interleukin (IL)-5 and IL-4 in peripheral blood of a patient fulfilling the diagnostic criteria of HES with associated serum hyper-IgE. We now extend this observation by describing identical findings in three additional patients, and we compare their clinical and biological parameters with five other patients with HES. Chromosomal abnormalities were detected in purified CD3-CD4+ Th2 cells from three patients, among whom one developed anaplastic null cell lymphoma. We therefore suggest that a careful search for T-lymphocyte clonality and cytogenetic changes should be included in the work-up of HES for adequate management.
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Hypereosinophilia: focus on clinical aspects
Revue medicale de Bruxelles, 1994Co-Authors: Elie CoganAbstract:Hypereosinophilia may be associated with various clinical disorders. The severity of Hypereosinophilia may be related to the underlying disease or to the possible deleterious effects of the eosinophils infiltrating most of the tissues, particularly the heart and the nervous system. Adverse reactions to drugs or other immunoallergic disorders are most often encountered. Among the parasitic diseases, helminthic infestations are especially incriminated. Cancers, autoimmune diseases and some T lymphoproliferative disorders represent the other reported conditions associated with Hypereosinophilia. The detection of interleukin-5 (the most important cytokine involved in the control of eosinophils production and maturation) may contribute to the knowledge of some pathological hypereosinophilic disorders. In the absence of a well defined responsible factor, the idiopathic hypereosinophilic syndrome will be considered. The pathogenic role of a T lymphocyte disorder need to be considered in some cases.
Grzegorz Helbig - One of the best experts on this subject based on the ideXlab platform.
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Imatinib for the treatment of hypereosinophilic syndromes
Expert review of clinical immunology, 2018Co-Authors: Grzegorz HelbigAbstract:Introduction: Hypereosinophilic syndromes (HES) encompass a group of disorders defined by sustained peripheral blood Hypereosinophilia >1500/mm3 and evidence of eosinophilia-associated organ impair...
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ORIGINAL PAPER Characteristics and clinical outcome of patients with Hypereosinophilia of undetermined significance
2016Co-Authors: Grzegorz Helbig, Marek Hus, Tomasz Francuz, Joanna Dziaczkowska-suszek, Anna SojaAbstract:Abstract The term ‘‘Hypereosinophilia of undetermined significance’ ’ (HEus) previously known as idiopathic, benign eosinophilia relates to patients who have a long-lasting, unexplained and asymptomatic blood HE. These patients have not been studied so far in terms of demo-graphic characteristics and clinical outcome. The aim of this study was to present the clinical characteristics and outcome of HEus patients. This is a retrospective, single-center study of 40 patients with HEus. All patients under-went the basic and specialized evaluations in order to rule out the most common causes of blood HE, but no abnor-malities were detected. Twelve patients with at least moderate blood Hypereosinophilia (defined as greater than 3.0 9 109/L) for more than 1-year duration were treated with corticosteroids (CS) to avoid end-organ damage. Twenty-one patients (52 %) had an increased leukocyte count at diagnosis. Median blood eosinophilia was 4.2 9 109/L (range 1.5–55.4). HE [ 3.0 9 109/L was demonstrated in 17 patients. 65 % of studied population had an increased serum IgE levels, whereas only 2 % demonstrated an increased serum vitamin B12 levels. A median bone marrow infiltration by eosinophils was 30.5 % (range 11–78.2). All treated patients responded promptly to CS and remained in complete remission while receiving low doses of CS (20 mg/day to 5 mg every 2-day). One patient developed hypereosinophilic syndrome (HES) after 11 years of follow-up. Further studies are needed to define risk factors of HES development. The use of CS for HEus patients is controversial and should be individualized
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characteristics and clinical outcome of patients with Hypereosinophilia of undetermined significance
Medical Oncology, 2014Co-Authors: Grzegorz Helbig, Marek Hus, Tomasz Francuz, Anna Soja, Joanna Dziaczkowskasuszek, Slawomira KyrczkrzemienAbstract:The term “Hypereosinophilia of undetermined significance” (HEus) previously known as idiopathic, benign eosinophilia relates to patients who have a long-lasting, unexplained and asymptomatic blood HE. These patients have not been studied so far in terms of demographic characteristics and clinical outcome. The aim of this study was to present the clinical characteristics and outcome of HEus patients. This is a retrospective, single-center study of 40 patients with HEus. All patients underwent the basic and specialized evaluations in order to rule out the most common causes of blood HE, but no abnormalities were detected. Twelve patients with at least moderate blood Hypereosinophilia (defined as greater than 3.0 × 109/L) for more than 1-year duration were treated with corticosteroids (CS) to avoid end-organ damage. Twenty-one patients (52 %) had an increased leukocyte count at diagnosis. Median blood eosinophilia was 4.2 × 109/L (range 1.5–55.4). HE > 3.0 × 109/L was demonstrated in 17 patients. 65 % of studied population had an increased serum IgE levels, whereas only 2 % demonstrated an increased serum vitamin B12 levels. A median bone marrow infiltration by eosinophils was 30.5 % (range 11–78.2). All treated patients responded promptly to CS and remained in complete remission while receiving low doses of CS (20 mg/day to 5 mg every 2-day). One patient developed hypereosinophilic syndrome (HES) after 11 years of follow-up. Further studies are needed to define risk factors of HES development. The use of CS for HEus patients is controversial and should be individualized.
Michel Goldman - One of the best experts on this subject based on the ideXlab platform.
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Hypereosinophilic syndrome: lymphoproliferative and myeloproliferative variants.
Seminars in respiratory and critical care medicine, 2006Co-Authors: Florence Roufosse, Michel Goldman, Elie CoganAbstract:Idiopathic hypereosinophilic syndrome is a largely heterogeneous disorder defined as persistent, marked Hypereosinophilia of unknown origin complicated by end-organ damage. Recent research in cellular and molecular biology has led to the characterization of distinct underlying hematological disorders, primitively involving cells of the myeloid or lymphoid lineage. The ability to classify many hypereosinophilic syndrome patients on the basis of pathogenesis of Hypereosinophilia has radically changed therapeutic perspectives. Indeed, imatinib mesylate has become first-line therapy for patients in whom the FIP1L1-PDGFRalpha fusion gene is detected, whereas corticosteroids remain the mainstay for management of patients in whom Hypereosinophilia is secondary to the overproduction of interleukin 5 by abnormal T-cells. Use of monoclonal anti-interleukin-5 antibodies in the latter group of patients has a strong rationale and could decrease cumulative corticosteroid doses and toxicity. As far as prognosis of these disease variants is concerned, hypereosinophilic syndrome patients with the FIP1L1-PDGFRalpha fusion gene may develop acute myelogenous (eosinophilic) leukemia, whereas those with clonal interleukin-5-producing T-cells have an increased risk of developing T-cell lymphoma. It is currently unclear whether timely therapeutic intervention in such patients could interfere with long-term progression toward malignant hematological disorders.
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clonal th2 cells associated with chronic Hypereosinophilia tarc induced ccr4 down regulation in vivo
European Journal of Immunology, 2001Co-Authors: Aurore De Lavareille, Florence Roufosse, Elie Cogan, Liliane Schandene, Patrick Stordeur, Michel GoldmanAbstract:We analyzed the expression of chemokine receptors on clonal Th2-type CD4(+)CD3(- )lymphocytes isolated from blood of two patients with chronic Hypereosinophilia. First, we observed that these Th2 cells express membrane CCR5 and CXCR4 but neither CCR3 nor CCR4 when analyzed immediately after purification. However, CCR4 appeared following culture in human serum-free medium, suggesting that it was down-regulated in vivo. Indeed, patient's serum, but not control human serum, strongly down-regulated CCR4 expression on cultured Th2 cells. As high levels of TARC, a CCR4 ligand, were detected in the serum of four hypereosinophilic patients with CD3(-)CD4(+) clonal Th2 cells, we evaluated the effect of TARC neutralization in this system. Addition of a neutralizing anti-TARC mAb inhibited CCR4 down-regulation by patient's serum, indicating that circulating TARC contributed to CCR4 down-regulation on Th2 cells in vivo. Clonal Th2 cells did not secrete high levels of TARC themselves but induced a sustained production of TARC by monocyte-derived dendritic cells, a phenomenon that was inhibited by addition of blocking mAb against IL-4 receptor. We conclude that high circulating levels of TARC in serum of patients with chronic Hypereosinophilia, most likely derived from antigen-presenting cells stimulated by Th2-type cytokines, induce down-regulation of CCR4 on Th2 cells in vivo.
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interferon α prevents spontaneous apoptosis of clonal th2 cells associated with chronic Hypereosinophilia
Blood, 2000Co-Authors: Liliane Schandene, Florence Roufosse, Elie Cogan, Aurore De Lavareille, Patrick Stordeur, Andre Efira, B Kennes, Michel GoldmanAbstract:A recent study identified a clonal expansion of CD3(-)CD4(+)cells secreting Th2-type cytokines in 4 patients with chronic Hypereosinophilia. Because interferon alpha (IFN-alpha) is used in the therapy of the idiopathic hypereosinophilic syndrome, the effects of this cytokine on the survival of clonal Th2 cells isolated from the blood of 2 patients were determined. First, these cells displayed a high rate of spontaneous apoptosis on culture in cytokine-free medium and were also sensitive to Fas-mediated apoptosis induced by soluble Fas ligand. Addition of IFN-alpha or interleukin-2 (IL-2) to culture medium resulted in significant protection against spontaneous but not Fas-induced apoptosis. Although spontaneous apoptosis of the clonal Th2 cells was clearly associated with down-regulation of both bcl-2 and bcl-x(L) levels, IFN-alpha had no significant effect on the expression of these antiapoptotic proteins, whereas addition of IL-2 resulted in higher levels of bcl-2. On the other hand, IFN-alpha decreased the numbers of cells with disrupted mitochondrial transmembrane potential both during spontaneous apoptosis and after exposure to protoporphyrin IX. Thus, IFN-alpha might promote the survival of clonal Th2 cells, an effect that could be relevant to the therapeutic approach for patients with chronic Hypereosinophilia caused by clonal expansion of Th2-type cells. (Blood. 2000;96:4285-4292)
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clonal th2 lymphocytes in patients with the idiopathic hypereosinophilic syndrome
British Journal of Haematology, 2000Co-Authors: Florence Roufosse, Michel Goldman, Liliane Schandene, Andre Efira, B Kennes, Catherine Sibille, Karen Willardgallo, Elie CoganAbstract:Idiopathic hypereosinophilic syndrome (HES) and Gleich's syndrome are related disorders characterized by persistent or recurrent Hypereosinophilia of unknown origin. Elevated IgE levels and polyclonal hypergammaglobulinaemia are considered as markers of benign outcome in this setting as they are generally associated with predominant cutaneous manifestations and favourable response to glucocorticoid therapy. In a previous study, we identified a clonal population of CD3-CD4+ Th2-like lymphocytes secreting interleukin (IL)-5 and IL-4 in peripheral blood of a patient fulfilling the diagnostic criteria of HES with associated serum hyper-IgE. We now extend this observation by describing identical findings in three additional patients, and we compare their clinical and biological parameters with five other patients with HES. Chromosomal abnormalities were detected in purified CD3-CD4+ Th2 cells from three patients, among whom one developed anaplastic null cell lymphoma. We therefore suggest that a careful search for T-lymphocyte clonality and cytogenetic changes should be included in the work-up of HES for adequate management.
M Capron - One of the best experts on this subject based on the ideXlab platform.
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Hypereosinophilia with abnormal t cells trisomy 7 and elevated tarc serum level
Haematologica, 2003Co-Authors: A S Roumier, Florence Roufosse, Nathalie Grardel, J L Lai, I Becqueriaux, Kamel Ghomari, A De Lavareille, L Prin, M CapronAbstract:The idiopathic hypereosinophilic syndrome (HES) is a rare heterogeneous disorder, characterized by persistent blood eosinophilia with possible organ involvement. We describe here the case of a 20-year-old atopic male presenting chronic Hypereosinophilia and eczema since childhood. Biological findings included Hypereosinophilia (9.5 x 10(9)/L), hyperlymphocytosis (10.9 x 10(9)/L), polyclonal hypergammaglobulinemia and elevated IgE serum level. Flow cytometric analysis of blood lymphoid cells showed a population of CD2+CD3-CD4+TCRab-TCRgd- lymphocytes. These cells displayed a Th0/Th2 cytokine profile, and a clonal TCR rearrangement pattern. A high serum TARC level was observed. Karyotype studies on blood stimulated culture or lymph nodes revealed a cellular hyperdiploid clone 47, XY, +7. To our knowledge, this chromosomal aberration has never been reported in such case.