Chief, Eosinophil Pathology Unit, LPD
The Eosinophil Pathology Unit conducts basic and translational research related to the role of the eosinophil and eosinophil activation in disease pathogenesis, with the ultimate goal of developing novel diagnostic tools and treatment approaches for hypereosinophilic syndromes and other conditions associated with marked eosinophilia, including helminth infection.
Using a translational approach, distinct clinical subgroups of patients with HES have been identified and characterized, including a myeloproliferative form of HES that includes FIP1L1/PDGFRA-positive chronic eosinophilic leukemia and an autosomal dominant form of familial eosinophilia that has been mapped to chromosome 5q31-33. Laboratory studies have focused on the role of eosinophils and eosinophil activation in producing the very different clinical presentations and outcomes of these disorders. Clinical trials using targeted therapies, including imatinib mesylate and monoclonal antibodies to IL-5, have provided additional insight into the etiology and pathogenesis of HES variants.
Eosinophilia is common in human helminth infection and may be associated with pathologic sequelae that mimic the clinical findings in HES, including tissue fibrosis and “allergic” manifestations. Furthermore, these manifestations may be produced or exacerbated by anthelminthic therapy. Prior research in the Helminth Immunology Section has demonstrated that these exacerbations are accompanied by an increase in IL-5, eosinophils, and markers of eosinophil activation. Consequently, a second major focus of our unit is to explore further the role of the eosinophil in post-treatment reactions and to use novel approaches to limit the pathology seen in these settings.
Clinicians in the Eosinophil Pathology Unit, along with others in the Laboratory of Parasitic Diseases, form the Clinical Parasitology Unit, which has played a major role in the training of physicians for careers in tropical medicine.
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Dr. Klion earned her B.A. from Princeton University and her M.D. from New York University School of Medicine. After completing a residency in internal medicine at Johns Hopkins University, she was a postdoctoral fellow in the Laboratory of Parasitic Diseases from 1989 to 1991. She completed her fellowship in infectious diseases at the University of Iowa Hospitals and Clinics in Iowa City, IA, where she was appointed an assistant professor in the division of infectious diseases prior to returning to the Laboratory of Parasitic Diseases in 1997 as a staff clinician. She became a tenure-track clinical investigator in the Laboratory of Parasitic Diseases in 2009.
Wilson TM, Maric I, Shukla J, Brown M, Santos C, Simakova O, Khoury P, Fay MP, Kozhich A, Kolbeck R, Metcalfe DD, Klion AD. IL-5 receptor a levels in patients with marked eosinophilia or mastocytosis. J Allergy Clin Immunol. 2011 July 13.
Roufosse F, de Lavareille A, Schandene L, Cogan E, Georgelas A, Wagner L, Xi L, Raffeld M, Goldman M, Gleich GJ, Klion A. Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome. J Allergy Clin Immunol. 2010 Oct;126(4):828-35.
Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PI, Parkin JM, Gleich GJ; Mepolizumab HES Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28.
Klion AD, Robyn J, Maric I, Fu W, Schmid L, Lemery S, Noel P, Law MA, Hartsell M, Talar-Williams C, Fay MP, Dunbar CE, Nutman TB. Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing. Blood. 2007 Nov 15;110(10):3552-6.
Maric I, Robyn J, Metcalfe DD, Fay MP, Carter M, Wilson T, Fu W, Stoddard J, Scott L, Hartsell M, Kirshenbaum A, Akin C, Nutman TB, Noel P, Klion AD. KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities. J Allergy Clin Immunol. 2007 Sep;120(3):680-7.
Klion AD, Law MA, Riemenschneider W, McMaster ML, Brown MR, Horne M, Karp B, Robinson M, Sachdev V, Tucker E, Turner M, Nutman TB. Familial eosinophilia: a benign disorder? Blood. 2004 Jun 1;103(11):4050-5.
Visit PubMed for a complete publication list.
A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Single-Dose Humanized Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa loa Infection, NCT01111305
Compassionate Use Mepolizumab in Subjects With Hypereosinophilic Syndrome (HES), NCT00244686
A Longitudinal Study of Familial Hypereosinophilia (FE): Natural History and Markers of Disease Progression, NCT00091871
Imatinib Mesylate To Treat Myeloproliferative Hypereosinophilic Syndrome, NCT00044304
Activation and Function of Eosinophils in Conditions With Blood or Tissue Eosinophilia, NCT00001406
Last Updated October 26, 2012