title: [Flow cytometry in the diagnosis of hemophagocytic lymphohistiocytosis in a case with fatal outcome].
abstract: Hemophagocytic lymphohistiocytosis is a multisystem inflammation, generated by the uncontrolled and excessive activation of cytotoxic T lymphocytes and natural killer cells. Severe immunodeficiency and generalized macrophage activation can often be detected in the background of this life threatening disorder. It is classified as a primary immunodeficiency. Functional abnormalities of the perforin protein or defects in granule secretory mechanisms are caused by gene mutations in most cases. Diagnostic criteria of hemophagocytic lymphohistiocytosis are the following: fever, splenomegaly, cytopenias affecting at least two of the 3 lineages in peripheral blood, hypertriglyceridemia and hyperferritinemia, elevated serum level of soluble interleukin-2 receptor (sCD25), hypofibrinogenemia, hemophagocytosis in bone marrow and decreased cytotoxic T cell and natural killer cell activity. In this case report the authors summarize the utility of functional flow cytometry in the diagnosis of hemophagocytic lymphohistiocytosis. Using flow cytometry, elevated intracellular perforin content, decreased killing activity of cytotoxic T cells and natural killer cells, and impaired cell surface expression of CD107a (LAMP1 protein) from in vitro stimulated blood lymphocytes were detected. Abnormal secretion of perforin was also demonstrated. Genetic testing revealed mutation of the MUNC 13-4 gene, which confirmed the base of the abnormal flow cytometric findings. This case report demonstrates the value of functional flow cytometry in the rapid diagnosis of genetically determined hemophagocytic lymphohistiocytosis, a condition in which early diagnosis is critical for optimal management. The authors emphasize the significance of functional flow cytometry in the differential diagnosis of immunodeficiencies.
authors.affiliation: Semmelweis Egyetem, Általános Orvostudományi Kar Genetikai, Sejt- és Immunbiológiai Intézet Budapest Nagyvárad tér 4. 1089.
authors.forename: Eva
authors.initials: E
authors.lastname: Pállinger
authors.affiliation: Semmelweis Egyetem, Általános Orvostudományi Kar II. Gyermekgyógyászati Klinika Budapest.
authors.forename: Dániel
authors.initials: D
authors.lastname: Erdélyi
authors.affiliation: Semmelweis Egyetem, Általános Orvostudományi Kar II. Gyermekgyógyászati Klinika Budapest.
authors.forename: Gábor
authors.initials: G
authors.lastname: Kovács
authors.affiliation: Egyesített Szt. István és Szt. László Kórház Budapest.
authors.forename: Gergely
authors.initials: G
authors.lastname: Kriván
authors.affiliation: Semmelweis Egyetem, Általános Orvostudományi Kar II. Gyermekgyógyászati Klinika Budapest.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Korponay
authors.affiliation: Semmelweis Egyetem, Általános Orvostudományi Kar II. Gyermekgyógyászati Klinika Budapest.
authors.forename: György
authors.initials: G
authors.lastname: Fekete
authors.affiliation: Semmelweis Egyetem, Általános Orvostudományi Kar II. Gyermekgyógyászati Klinika Budapest.
authors.forename: András
authors.initials: A
authors.lastname: Szabó
authors.affiliation: Semmelweis Egyetem, Általános Orvostudományi Kar Genetikai, Sejt- és Immunbiológiai Intézet Budapest Nagyvárad tér 4. 1089.
authors.forename: András
authors.initials: A
authors.lastname: Falus
authors.affiliation: Semmelweis Egyetem, Általános Orvostudományi Kar II. Gyermekgyógyászati Klinika Budapest.
authors.forename: Beáta
authors.initials: B
authors.lastname: Dérfalvi
mesh_terms: D016572:Cyclosporine / Q000627:therapeutic use; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007223:Infant; D007694:Killer Cells, Natural / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D009154:Mutation; D054353:Perforin / Q000235:genetics / Q000378:metabolism*
chemical_list: D016756:Immunoglobulins, Intravenous; D052118:Lysosomal-Associated Membrane Protein 1; D054353:Perforin; D016572:Cyclosporine
keywords: flow cytometry; haemophagocytás lymphohistiocytosis; hemophagocytic lymphohistiocytosis; macrophagaktiváció; macrophage activation; primary immunodeficiency; primer immundeficientia; áramlási citometria