title: Clinical aspects, immunologic assessment, and genetic analysis in Taiwanese children with hemophagocytic lymphohistiocytosis.
abstract: BACKGROUND
  Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by immune disturbance associated with certain genetic defects. This study aimed to define the clinical spectrum, immunology, and candidate genes in HLH in Taiwanese patients.
  
  
  METHODS
  The medical records of children who met the updated diagnostic criteria and had confirmed hemophagocytosis by bone marrow aspiration between 1992 and 2007 were retrospectively evaluated. The clinical course and prognosis were analyzed. Quantitative immunoglobulin, lymphocyte subsets, cytotoxicity to K562 cells, intracellular natural killer perforin expression, and candidate genes including SH2D1A, PFR1, Mun13-4, and STX11 genes were also investigated.
  
  
  RESULTS
  Thirty-two patients (16 male) were evaluated during the 15-year period. The underlying diseases were acute lymphoblastic leukemia, systemic lupus erythematosus, natural killer malignancy, juvenile idiopathic arthritis, and Chediak-Higashi syndrome. Epstein-Barr virus (EBV)-associated HLH was present in 12 patients, 6 of whom died, while 12 of 20 non-EBV-associated patients died despite aggressive polychemotherapy. Extreme immunoglobulin values occurred in 3 fatal cases. There was decreasing percentage of CD4, CD1656, and B-memory cells and increasing CD8, activated lymphocyte, and T-memory cells among the patients. Cytotoxicity in 14 patients and intracellular perforin expression in 13 were diminished but restored to borderline normal range during the convalescent stage. None of the mutations of SH2D1A, PFR1, Mun13-4, and STX11 genes were found.
  
  
  CONCLUSIONS
  In the treatment of Taiwanese HLH patients, aggressive chemotherapy in EBV-associated patients and stem cell transplantation in non-EBV-associated patients are recommended to improve survival. Individualized immune dysregulation instead of the well-known candidate genetic mutations can explain the genetic variation in our cohort.
authors.affiliation: Primary Immunodeficiency Care and Research (PICAR) Institute, and Departments of Chang Gung Children's and Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. wen2707@hotmail.com
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Lee
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: Tang-Her
authors.initials: TH
authors.lastname: Jaing
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chen
authors.forename: Shin-Pai
authors.initials: SP
authors.lastname: Li
authors.forename: Jing-Long
authors.initials: JL
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007223:Infant; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D008297:Male; D054353:Perforin / Q000096:biosynthesis; D012189:Retrospective Studies; D013624:Taiwan
chemical_list: D007136:Immunoglobulins; D054353:Perforin