title: Primary and secondary hemophagocytic lymphohistiocytosis have different patterns of T-cell activation, differentiation and repertoire.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome characterized by hyperactivation of lymphocytes and histiocytes. T cells play a key role in HLH pathogenesis, but their differentiation pattern is not well characterized in patients with active HLH. We compared T-cell activation patterns between patients with familial HLH (1°HLH), 2°HLH without apparent infectious trigger (2°HLH) and 2°HLH induced by a viral infection (2°V-HLH). Polyclonal CD8+T cells are highly activated in 1°HLH and 2°V-HLH, but less in 2°HLH as assessed by HLA-DR expression and marker combination with CD45RA, CCR7, CD127, PD-1 and CD57. Absence of increased HLA-DR expression on T cells excluded active 1° HLH with high sensitivity and specificity. A high proportion of polyclonal CD127-CD4+T cells expressing HLA-DR, CD57, and perforin is a signature of infants with 1°HLH, much less prominent in virus-associated 2°HLH. The similar pattern and extent of CD8+T-cell activation compared to 2° V-HLH is compatible with a viral trigger of 1°HLH. However, in most 1°HLH patients no triggering infection was documented and the unique activation of cytotoxic CD4+T cells indicates that the overall T-cell response in 1°HLH is different. This may reflect different pathways of pathogenesis of these two HLH variants.
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.|Faculty of Biology, University of Freiburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ammann
authors.affiliation: Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Lehmberg
authors.affiliation: Center for Diagnostic, University Medical Center Hamburg Eppendorf, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Zur Stadt
authors.affiliation: Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Germany.
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Rensing-Ehl
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.|Center for Pediatrics, Department of Pediatric Hematology and Oncology, University Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Klemann
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.|Center for Pediatrics, Department of Pediatric Hematology and Oncology, University Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Heeg
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.|Center for Pediatrics, Department of Pediatric Hematology and Oncology, University Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bode
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Fuchs
authors.affiliation: Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.|Center for Pediatrics, Department of Pediatric Hematology and Oncology, University Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehl
mesh_terms: D018959:CD57 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000209:etiology / Q000276:immunology*; D008297:Male; D054353:Perforin / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014777:Virus Diseases / Q000150:complications / Q000175:diagnosis / Q000276:immunology*
chemical_list: D018959:CD57 Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell; D054353:Perforin
keywords: HLA-DR; Hemophagocytic lymphohistiocytosis; Perforin; Primary HLH; Secondary HLH; T-cell activation