Hemophagocytic lymphohistiocytosis: diagnosis, pathophysiology, treatment, and future perspectives.
Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease in which the immune system becomes overactive due to its inability to effectively respond to infections and/or shut down the immune response to such infections. The discovery of genetic defects in the secretory pathway of natural killer (NK) cells and cytotoxic T cells in some patients with this disease has raised important questions of the role of cytotoxic cells in the control of infections and in immune regulation. This review will give a brief overview of the clinical presentation and accepted treatment of HLH. Furthermore, it will give an in-depth review into the known genetic defects and current knowledge of the pathophysiology of this disorder, and will highlight recent evidence suggesting that cytotoxic defects in CD4+ T regulatory cells may contribute to the pathogenesis of HLH.
Verbsky
James W
JW
Division of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
Grossman
William J
WJ
D000818:Animals; D004247:DNA / Q000235:genetics; D003937:Diagnosis, Differential; D006801:Humans; D007111:Immunity, Cellular; D007155:Immunologic Factors / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D015398:Signal Transduction / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D004247:DNA