title: Impairment of Immune Function in Children with Familial Hemophagocytic Lymphohistiocytosis.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is a severe systemic syndrome associated with hyperactivation of macrophages and impaired regulation of the immune system. Two forms of HLH are currently recognized: genetically determined or familial (FHLH), and secondarily developed in the course of primary diseases, like autoimmune disorders, rheumatoid disorders, cancers, or infections. In the Polish population, FHLH is rather rare. The aim of the present study was to assess the immune function in a group of children with clinical symptoms suggesting FHLH. Forty five children with suspected HLH of the median age of 4 years and 15 healthy children, taken as a control group, were enrolled into the study. All presented results were obtained with the use of flow cytometry. In the HLH group, there were only three cases identified with the UNC13D gene mutation responsible for the FHLH3 phenotype. Another four children, without known mutation, were classified as FHLH because of frequent recurrence of the disease. In all cases of FHLH, cell cytotoxicity was impaired compared with healthy children (p = 0.003). Perforin expression in FHLH was normal or higher than that observed in controls (p = 0.09). In case of patients with mutation in the Munc13 protein, degranulation was lower than that in healthy children (<5 %). The findings of this study demonstrate that children with known mutations responsible for the FHLH development are immunocompromised. However, it requires further elucidation whether the presence of currently unknown mutations could lead to a similar phenotype.
authors.affiliation: Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Warsaw Medical University, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Popko
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Jasińska
authors.affiliation: Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Warsaw Medical University, Warsaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Górska
authors.affiliation: Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Warsaw Medical University, Warsaw, Poland.
authors.forename: U
authors.initials: U
authors.lastname: Demkow
authors.affiliation: Department of Pediatrics, Oncology and Hematology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Balwierz
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Endocrinology, Gdansk Medical University, Gdansk, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Maciejka-Kembłowska
authors.affiliation: Department of Pediatric Hematology and Oncology, Regional Children's Hospital, Olsztyn, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Badowska
authors.affiliation: Department of Pediatric Oncology and Hematology, Poznan Medical University, Poznan, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Wachowiak
authors.affiliation: Department of Pediatrics, Hematology, Oncology and Transplantology, Children's Hospital, Lublin, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Drabko
authors.affiliation: Department of Pediatrics, Hematology and Oncology, Warsaw Medical University, 63A Żwirki i Wigury St., 02-091, Warsaw, Poland. iwona.malinowska@wum.edu.pl.
authors.forename: I
authors.initials: I
authors.lastname: Malinowska
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics* / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation
chemical_list: D052118:Lysosomal-Associated Membrane Protein 1; D008565:Membrane Proteins; C507969:UNC13D protein, human
keywords: Cytotoxicity; Degranulation; Hemophagocytic lymphohistiocytosis; Natural killer cells; Perforin