Angeborene hämophagozytische Lymphohistiozytose (HLH).
Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal immune disorder characterized by uncontrolled lymphocyte- and macrophage-activation. The resulting hypercytokinemia and cell infiltration of organs lead to the clinical and laboratory features of HLH. Viral infections and other triggers can induce both, inherited and acquired forms of HLH. Disease-causing mutations in the genes encoding perforin (PRF1, FHL2), munc13-4 (UNC13D, FHL3), syntaxin 11 (STX11, FHL4), and munc18-2 (UNC18-2/STXBP2, FHL5) have been previously identified in Familial Hemophagocyic Lymphohistiocytosis (FHL), whereas mutation in RAB27A and LYST account for Griscelli syndome type 2 and Chediak-Higashi syndrome, respectively. These genes all encode proteins which are involved in the cytotoxic activity of lymphocytes. The inability of activated cytotoxic cells to clear antigen-presenting targets results in sustained immune stimulation, likely accounting for the unremitting polyclonal CD8 T-cell activation and hyperimmune reaction which characterizes FHL. Treatment of HLH consists of elimination of the trigger and immunosuppressive treatment in order to induce remission from the uncontrolled inflammation. Allogeneic hematopoietic stem cell transplantation can be indicated in the inherited forms of HLH.
Pachlopnik Schmid
J
J
Children's Hospital, University of Zurich, Steinwiesstrasse 75, Zurich, Switzerland. janapachlopnik@hotmail.com
de Saint Basile
G
G
D002648:Child; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008262:Macrophage Activation / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051938:Munc18 Proteins / Q000235:genetics; D054353:Perforin / Q000235:genetics; D011379:Prognosis; D050765:Qa-SNARE Proteins / Q000235:genetics; D014777:Virus Diseases / Q000150:complications
D008565:Membrane Proteins; D051938:Munc18 Proteins; D050765:Qa-SNARE Proteins; C541732:STX11 protein, human; C497940:STXBP2 protein, human; C507969:UNC13D protein, human; D054353:Perforin