title: Episodic angioedema with eosinophilia (Gleich syndrome) is a multilineage cell cycling disorder.
abstract: Episodic angioedema with eosinophilia (Gleich syndrome) is a rare disorder characterized by episodes of angioedema and eosinophilia that occur at monthly intervals and resolve spontaneously without therapy. Despite the striking periodicity of this disorder, its similarity to other cyclic hematopoietic disorders with multilineage involvement has not been assessed. To characterize the involvement of cell lineages in the etiology and pathogenesis of episodic angioedema with eosinophilia, four subjects were evaluated by blood counts and other analyses over the course of 1-2 months. Surface marker expression was assessed on T cells by flow cytometry and clonality by polymerase chain reaction. Intracellular cytokine evaluation, bone marrow and skin biopsies were performed during different parts of the cycle. Cycling of multiple cell lineages, including neutrophils, lymphocytes and eosinophils, was observed in the four subjects with the disorder with a periodicity of 25-35 days. An aberrant CD3(-)CD4(+) T-cell population was detected in all four subjects, and T-cell receptor rearrangement studies showed a clonal pattern in three subjects. A peak of type II cytokines was detected in the serum of subjects prior to the onset of symptoms and eosinophil cycling and corresponded to ex-vivo type II cytokines detected intracellularly in CD3(+)CD4(+)CD154(+) T cells. Although the etiology of episodic angioedema with eosinophilia is not yet known, multiple lineages, including lymphocytes, neutrophils and mast cells, are involved and may be related to disease pathogenesis. Whether these cells act directly or promote eosinophilia and eosinophil activation remains to be elucidated. All subjects gave informed consent and were evaluated under an Institutional Review Board-approved protocol (NCT00001406).
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD khouryp@niaid.nih.gov.
authors.forename: Paneez
authors.initials: P
authors.lastname: Khoury
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Herold
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Alpaugh
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD.
authors.forename: Ellen
authors.initials: E
authors.lastname: Dinerman
authors.affiliation: Laboratory of Parasitic Diseases, Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD.
authors.forename: Nicole
authors.initials: N
authors.lastname: Holland-Thomas
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stoddard
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Shakuntala
authors.initials: S
authors.lastname: Gurprasad
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Irina
authors.initials: I
authors.lastname: Maric
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.
authors.forename: Olga
authors.initials: O
authors.lastname: Simakova
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Virginia Commonwealth University, Richmond, VA.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schwartz
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD.
authors.forename: Juelia
authors.initials: J
authors.lastname: Fong
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Chyi-Chia Richard
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xi
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Zengfeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.affiliation: Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Klion
mesh_terms: D000328:Adult; D000799:Angioedema / Q000150:complications / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D015703:Antigens, CD / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D019070:Cell Lineage / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004802:Eosinophilia / Q000150:complications / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010507:Periodicity; D012867:Skin / Q000276:immunology / Q000473:pathology; D013577:Syndrome; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD; D016207:Cytokines