title: Immunologic difference between hypersensitivity to mosquito bite and hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus infection.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, virus-triggered immune disease. Hypersensitivity to mosquito bite (HMB), a presentation of Chronic Active Epstein-Barr Virus infection (CAEBV), may progress to HLH. This study aimed to investigate the immunologic difference between the HMB episodes and the HLH episodes associated with EBV infection. Immunologic changes of immunoglobulins, lymphocyte subsets, cytotoxicity, intracellular perforin and granzyme expressions, EBV virus load and known candidate genes for hereditary HLH were evaluated and compared. In 12 HLH episodes (12 patients) and 14 HMB episodes (4 patients), there were both decreased percentages of CD4+ and CD8+ and increased memory CD4+ and activated (CD2+HLADR+) lymphocytes. In contrast to HMB episodes that had higher IgE levels and EBV virus load predominantly in NK cells, those HLH episodes with virus load predominantly in CD3+ lymphocyte had decreased perforin expression and cytotoxicity that were recovered in the convalescence period. However, there was neither significant difference of total virus load in these episodes nor candidate genetic mutations responsible for hereditary HLH. In conclusion, decreased perforin expression in the HLH episodes with predominant-CD3+ EBV virus load is distinct from those HMB episodes with predominant-NK EBV virus load. Whether the presence of non-elevated memory CD4+ cells or activated lymphocytes (CD2+HLADR+) increases the mortality rate in the HLH episodes remains to be further warranted through larger-scale studies.
authors.affiliation: Primary Immunodeficiency Care And Research (PICAR) Institute, Chang Gung Children's Hospital, Taoyuan, Taiwan ; Department of Pediatrics, Division of Allergy Asthma and Rheumatology, Chang Gung Children's Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Lee
authors.forename: Jainn-Jim
authors.initials: JJ
authors.lastname: Lin
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Syh-Jae
authors.initials: SJ
authors.lastname: Lin
authors.forename: Tang-Her
authors.initials: TH
authors.lastname: Jaing
authors.forename: Shih-Hsiang
authors.initials: SH
authors.lastname: Chen
authors.forename: Iou-Jih
authors.initials: IJ
authors.lastname: Hung
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Yang
authors.forename: Chin-Jung
authors.initials: CJ
authors.lastname: Chen
authors.forename: Yhu-Chering
authors.initials: YC
authors.lastname: Huang
authors.forename: Shin-Pai
authors.initials: SP
authors.lastname: Li
authors.forename: Jing-Long
authors.initials: JL
authors.lastname: Huang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D009033:Culicidae / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D007299:Insect Bites and Stings / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
chemical_list: D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C507969:UNC13D protein, human; D054353:Perforin; D053804:Granzymes