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K. Beutel, U. Gross-Wieltsch, T. Wiesel, U. Stadt, G. Janka, H. Wagner (2009)
Infection of T lymphocytes in Epstein‐Barr virus‐associated hemophagocytic lymphohistiocytosis in children of non‐Asian originPediatric Blood & Cancer, 53
N. Mahlaoui, M. Ouachée-Chardin, G. Basile, B. Neven, C. Picard, S. Blanche, A. Fischer (2007)
Immunotherapy of Familial Hemophagocytic Lymphohistiocytosis With Antithymocyte Globulins: A Single-Center Retrospective Report of 38 PatientsPediatrics, 120
Nichola Cooper, K. Rao, Nick Goulden, D. Webb, P. Amrolia, P. Veys (2008)
The use of reduced-intensity stem cell transplantation in haemophagocytic lymphohistiocytosis and Langerhans cell histiocytosisBone Marrow Transplantation, 42
A. Ravelli, S. Magni-Manzoni, A. Pistorio, C. Besana, T. Foti, N. Ruperto, S. Viola, A. Martini (2005)
Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.The Journal of pediatrics, 146 5
A. Filipovich (2008)
Hemophagocytic lymphohistiocytosis and other hemophagocytic disorders.Immunology and allergy clinics of North America, 28 2
Jenny Chia, Kim Yeo, J. Whisstock, M. Dunstone, J. Trapani, I. Voskoboinik (2009)
Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancerProceedings of the National Academy of Sciences, 106
N. Wulffraat, G. Rijkers, E. Elst, R. Brooimans, W. Kuis (2003)
Reduced perforin expression in systemic juvenile idiopathic arthritis is restored by autologous stem-cell transplantation.Rheumatology, 42 2
U. Titze, G. Janka, E. Schneider, F. Prall, D. Haffner, Carl Classen (2009)
Hemophagocytic lymphohistiocytosis and Kawasaki disease: Combined manifestation and differential diagnosisPediatric Blood & Cancer, 53
G. Janka (2006)
Familial and acquired hemophagocytic lymphohistiocytosisEuropean Journal of Pediatrics, 166
S. Marcenaro, Federico Gallo, S. Martini, A. Santoro, G. Griffiths, M. Aricò, L. Moretta, D. Pende (2006)
Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease.Blood, 108 7
C. Booth, Kimberly Gilmour, P. Veys, A. Gennery, M. Slatter, H. Chapel, Paul Heath, Colin Steward, O. Smith, A. O'meara, Hilary Kerrigan, N. Mahlaoui, M. Cavazzana‐Calvo, A. Fischer, D. Moshous, S. Blanche, J. Schmid, S. Latour, G. Saint-Basile, M. Albert, G. Notheis, N. Rieber, B. Strahm, H. Ritterbusch, A. Lankester, Nico Hartwig, I. Meyts, A. Plebani, A. Soresina, A. Finocchi, C. Pignata, E. Cirillo, S. Bonanomi, C. Peters, K. Kałwak, S. Pašić, P. Sedláček, J. Jazbec, H. Kanegane, Kim Nichols, I. Hanson, N. Kapoor, E. Haddad, M. Cowan, S. Choo, Joanne Smart, Peter Arkwright, H. Gaspar (2011)
X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease.Blood, 117 1
J. Farquhar, A. Claireaux (1952)
Familial Haemophagocytic ReticulosisBritish Medical Journal, 2
M. Aricò, L. Nespoli, R. Maccario, D. Montagna, F. Bonetti, D. Caselli, G. Burgio (1988)
Natural cytotoxicity impairment in familial haemophagocytic lymphohistiocytosis.Archives of Disease in Childhood, 63
Y. Bryceson, E. Rudd, C. Zheng, J. Edner, D. Ma, Stephanie Wood, A. Bechensteen, J. Boelens, T. Celkan, R. Farah, K. Hultenby, J. Winiarski, P. Roche, M. Nordenskjöld, J. Henter, Eric Long, H. Ljunggren (2007)
Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients.Blood, 110 6
Y. Osugi, J. Hara, S. Tagawa, K. Takai, G. Hosoi, Y. Matsuda, H. Ohta, H. Fujisaki, Michiko Kobayashi, N. Sakata, K. Kawa-ha, S. Okada, A. Tawa (1997)
Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis.Blood, 89 11
J. Schmid, Chen-Hsuan Ho, F. Chrétien, Juliette Lefebvre, G. Pivert, M. Kosco-Vilbois, W. Ferlin, F. Geissmann, A. Fischer, G. Basile (2009)
Neutralization of IFNγ defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient miceEMBO Molecular Medicine, 1
J. Schmid, D. Canioni, D. Moshous, F. Touzot, N. Mahlaoui, F. Hauck, H. Kanegane, E. López-Granados, E. Mejstrikova, I. Pellier, L. Galicier, C. Galambrun, V. Barlogis, P. Bordigoni, A. Fourmaintraux, M. Hamidou, A. Dabadie, F. Deist, F. Haerynck, M. Ouachée-Chardin, P. Rohrlich, J. Stéphan, C. Lenoir, S. Rigaud, N. Lambert, M. Milili, C. Schiff, H. Chapel, C. Picard, G. Basile, S. Blanche, A. Fischer, S. Latour (2011)
Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency).Blood, 117 5
M. Ouachée-Chardin, C. Elie, G. Basile, F. Deist, N. Mahlaoui, C. Picard, B. Neven, J. Casanova, M. Tardieu, M. Cavazzana‐Calvo, S. Blanche, A. Fischer (2006)
Hematopoietic Stem Cell Transplantation in Hemophagocytic Lymphohistiocytosis: A Single-Center Report of 48 PatientsPediatrics, 117
R. Hotchkiss, D. Nicholson (2006)
Apoptosis and caspases regulate death and inflammation in sepsisNature Reviews Immunology, 6
C. Allen, Xiaoying Yu, C. Kozinetz, K. McClain (2008)
Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosisPediatric Blood & Cancer, 50
G. Basile, Gaël Ménasché, A. Fischer (2010)
Molecular mechanisms of biogenesis and exocytosis of cytotoxic granulesNature Reviews Immunology, 10
R. Marsh, G. Vaughn, Mi‐Ok Kim, Dandan Li, S. Jodele, S. Joshi, P. Mehta, S. Davies, M. Jordan, J. Bleesing, A. Filipovich (2010)
Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation.Blood, 116 26
J. Stinchcombe, G. Bossi, G. Griffiths (2004)
Linking Albinism and Immunity: The Secrets of Secretory LysosomesScience, 305
J. Henter, A. Horne, M. Aricò, R. Egeler, A. Filipovich, S. Imashuku, S. Ladisch, K. McClain, D. Webb, J. Winiarski, G. Janka (2007)
HLH‐2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosisPediatric Blood & Cancer, 48
A. Horne, C. Zheng, I. Lorenz, M. Löfstedt, S. Montgomery, G. Janka, J. Henter, E. Schneider (2005)
Subtyping of natural killer cell cytotoxicity deficiencies in haemophagocytic lymphohistocytosis provides therapeutic guidanceBritish Journal of Haematology, 129
A. Karras, E. Thervet, C. Legendre (2004)
Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literatureTransplantation, 77
A. Gurgey, S. Aytaç, G. Balta, K. Oguz, F. Gumruk (2008)
Central Nervous System Involvement in Turkish Children With Primary Hemophagocytic LymphohistiocytosisJournal of Child Neurology, 23
A. Horne, G. Janka, R. Egeler, H. Gadner, S. Imashuku, S. Ladisch, F. Locatelli, S. Montgomery, D. Webb, J. Winiarski, A. Filipovich, J. Henter (2005)
Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosisBritish Journal of Haematology, 129
U. Stadt, S. Schmidt, B. Kasper, K. Beutel, A. Diler, J. Henter, H. Kabisch, R. Schneppenheim, P. Nürnberg, G. Janka, H. Hennies (2005)
Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11.Human molecular genetics, 14 6
A. Abdelkefi, W. Jamil, L. Torjman, S. Ladeb, H. Ksouri, A. Lakhal, A. Hassen, A. Abdeladhim, T. Othman (2009)
Hemophagocytic syndrome after hematopoietic stem cell transplantation: a prospective observational studyInternational Journal of Hematology, 89
J. Feldmann, I. Callebaut, G. Raposo, S. Certain, D. Bacq, C. Dumont, N. Lambert, M. Ouachée-Chardin, G. Chédeville, H. Tamary, V. Minard-Colin, E. Vilmer, S. Blanche, F. Deist, A. Fischer, G. Basile (2003)
Munc13-4 Is Essential for Cytolytic Granules Fusion and Is Mutated in a Form of Familial Hemophagocytic Lymphohistiocytosis (FHL3)Cell, 115
U. Stadt, J. Rohr, W. Seifert, F. Koch, S. Grieve, Julia Pagel, J. Strauss, B. Kasper, G. Nürnberg, C. Becker, A. Maul‐Pavicic, K. Beutel, G. Janka, G. Griffiths, S. Ehl, H. Hennies (2009)
Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11.American journal of human genetics, 85 4
F. Ménard, C. Besson, P. Rincé, O. Lambotte, T. Lazure, D. Canioni, O. Hermine, P. Brousset, Antoine Martin, P. Gaulard, M. Raphaël, C. Larroche (2008)
Hodgkin lymphoma-associated hemophagocytic syndrome: a disorder strongly correlated with Epstein-Barr virus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 47 4
S. Imashuku (2011)
Treatment of Epstein-Barr Virus-related Hemophagocytic Lymphohistiocytosis (EBV-HLH); Update 2010Journal of Pediatric Hematology/Oncology, 33
Prof. Janka (2009)
Hemophagocytic Lymphohistiocytosis: When the Immune System Runs AmokKlinische Padiatrie, 221
R. Clementi, F. Locatelli, L. Dupré, A. Garaventa, L. Emmi, M. Bregni, G. Cefalo, A. Moretta, C. Danesino, M. Comis, A. Pession, U. Ramenghi, R. Maccario, M. Aricò, M. Roncarolo (2004)
A proportion of patients with lymphoma may harbor mutations of the perforin gene.Blood, 105 11
M. Jordan, David Hildeman, J. Kappler, P. Marrack (2004)
An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder.Blood, 104 3
Kazuhiro Kogawa, Susan Lee, J. Villanueva, Daniel Marmer, Janos Sumegi, A. Filipovich (2002)
Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members.Blood, 99 1
K. Sandrock, L. Nakamura, T. Vraetz, K. Beutel, S. Ehl, B. Zieger (2010)
Platelet secretion defect in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL-5).Blood, 116 26
J. Rohr, K. Beutel, A. Maul‐Pavicic, T. Vraetz, J. Thiel, K. Warnatz, Ilka Bondzio, U. Gross-Wieltsch, Michael Schündeln, B. Schütz, W. Woessmann, A. Groll, B. Strahm, Julia Pagel, C. Speckmann, G. Janka, G. Griffiths, K. Schwarz, U. Stadt, S. Ehl (2010)
Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseasesHaematologica, 95
J. Henter, AnnaCarin Samuelsson-Horne, M. Aricò, R. Egeler, G. Elinder, A. Filipovich, H. Gadner, S. Imashuku, D. Komp, S. Ladisch, D. Webb, G. Janka (2002)
Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation.Blood, 100 7
R. Marsh, J. Bleesing, A. Filipovich (2010)
Using flow cytometry to screen patients for X-linked lymphoproliferative disease due to SAP deficiency and XIAP deficiency.Journal of immunological methods, 362 1-2
L. Fardet, O. Lambotte, J. Meynard, W. Kamouh, L. Galicier, C. Marzac, A. Labarthe, J. Cabane, C. Lebbé, P. Coppo, J. Molina, V. Martinez (2010)
Reactive haemophagocytic syndrome in 58 HIV-1-infected patients: clinical features, underlying diseases and prognosisAIDS, 24
Marjorie Côte, M. Ménager, Agathe Burgess, N. Mahlaoui, C. Picard, C. Schaffner, Fahad Al‐Manjomi, M. Al-Harbi, A. Alangari, F. Deist, A. Gennery, Nathalie Prince, Astrid Cariou, P. Nitschké, U. Blank, G. El-Ghazali, Gaël Ménasché, S. Latour, A. Fischer, G. Basile (2009)
Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells.The Journal of clinical investigation, 119 12
I. Ueda, Y. Kurokawa, K. Koike, S. Ito, A. Sakata, Tsutomu Matsumora, T. Fukushima, A. Morimoto, E. Ishii, S. Imashuku (2007)
Late‐onset cases of familial hemophagocytic lymphohistiocytosis with missense perforin gene mutationsAmerican Journal of Hematology, 82
S. Stepp, R. Dufourcq-Lagelouse, F. Deist, F. Deist, Sadhna Bhawan, S. Certain, P. Mathew, J. Henter, M. Bennett, A. Fischer, A. Fischer, G. Basile, Vinay Kumar (1999)
Perforin gene defects in familial hemophagocytic lymphohistiocytosis.Science, 286 5446
E. Sieni, V. Cetica, Alessandra Santoro, K. Beutel, Elena Mastrodicasa, Marie Meeths, Benedetta Ciambotti, Francesca Brugnolo, U. Stadt, D. Pende, Lorenzo Moretta, Gillian Griffiths, J. Henter, G. Janka, M. Aricò (2011)
Genotype–phenotype study of familial haemophagocytic lymphohistiocytosis type 3Journal of Medical Genetics, 48
S. Vastert, R. Wijk, L. D'urbano, K. Vooght, W. Jager, A. Ravelli, S. Magni-Manzoni, A. Insalaco, E. Cortis, W. Solinge, B. Prakken, N. Wulffraat, F. Benedetti, W. Kuis (2010)
Mutations in the perforin gene can be linked to macrophage activation syndrome in patients with systemic onset juvenile idiopathic arthritis.Rheumatology, 49 3
P. Miettunen, Aru Narendran, Aarthi Jayanthan, Edward Behrens, R. Cron (2011)
Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients.Rheumatology, 50 2
K. Nagafuji, A. Nonami, T. Kumano, Y. Kikushige, G. Yoshimoto, K. Takenaka, K. Shimoda, S. Ohga, M. Yasukawa, H. Horiuchi, E. Ishii, M. Harada (2007)
Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis.Haematologica, 92 7
Kejian Zhang, J. Biroschak, D. Glass, S. Thompson, T. Finkel, M. Passo, B. Binstadt, A. Filipovich, A. Grom (2008)
Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms.Arthritis and rheumatism, 58 9
A. Grom, E. Mellins (2010)
Macrophage activation syndrome: advances towards understanding pathogenesisCurrent Opinion in Rheumatology, 22
J. Niece, Z. Rogers, Naveed Ahmad, A. Langevin, K. McClain (2010)
Hemophagocytic lymphohistiocytosis in Texas: Observations on ethnicity and racePediatric Blood & Cancer, 54
A. Trizzino, U. Stadt, I. Ueda, K. Risma, G. Janka, E. Ishii, K. Beutel, J. Sumegi, S. Cannella, D. Pende, A. Mian, J. Henter, G. Griffiths, A. Santoro, A. Filipovich, M. Aricò (2007)
Genotype–phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutationsJournal of Medical Genetics, 45
A. Grom, J. Villanueva, Susan Lee, E. Goldmuntz, M. Passo, A. Filipovich (2003)
Natural killer cell dysfunction in patients with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome.The Journal of pediatrics, 142 3
P. Stepensky, M. Weintraub, A. Yanir, S. Revel-Vilk, F. Krux, K. Huck, R. Linka, A. Shaag, O. Elpeleg, A. Borkhardt, I. Resnick (2011)
IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approachHaematologica, 96
E. Behrens, T. Beukelman, M. Paessler, R. Cron (2007)
Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis.The Journal of rheumatology, 34 5
I. Voskoboinik, V. Sutton, A. Ciccone, C. House, Jenny Chia, P. Darcy, H. Yagita, J. Trapani (2007)
Perforin activity and immune homeostasis: the common A91V polymorphism in perforin results in both presynaptic and postsynaptic defects in function.Blood, 110 4
I. Voskoboinik, M. Smyth, J. Trapani (2006)
Perforin-mediated target-cell death and immune homeostasisNature Reviews Immunology, 6
J. Stéphan, I. Koné-Paut, C. Galambrun, R. Mouy, B. Bader-Meunier, A. Prieur (2001)
Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients.Rheumatology, 40 11
H. Kawaguchi, T. Miyashita, Hermann Herbst, G. Niedobitek, M. Asada, M. Tsuchida, R. Hanada, A. Kinoshita, M. Sakurai, N. Kobayashi, S. Mizutani (1993)
Epstein-Barr virus-infected T lymphocytes in Epstein-Barr virus-associated hemophagocytic syndrome.The Journal of clinical investigation, 92 3
U. Emmenegger, A. Reimers, U. Frey, C. Fux, F. Bihl, D. Semela, P. Cottagnoud, A. Cerny, P. Spaeth, K. Neftel (2002)
Reactive macrophage activation syndrome: a simple screening strategy and its potential in early treatment initiation.Swiss medical weekly, 132 17-18
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome in which an uncontrolled and ineffective immune response, triggered in most cases by infectious agents, leads to severe hyperinflammation. Familial forms of HLH (FHL), which are increasingly found also in adolescents and adults, are due to genetic defects leading to impaired function of natural killer cells and cytotoxic T cells. These mutations occur either in the perforin gene or in genes important for the exocytosis of cytotoxic granules. Cytotoxic granules contain perforin and granzymes, which induce apoptosis upon entering (infected) target cells. Additionally, perforin is important for the downregulation of the immune response. Acquired forms of HLH are encountered in association with (usually) viral infections, autoinflammatory//autoimmune diseases, malignant diseases, and acquired immune deficiency states (e.g., after organ transplantation). Treatment of HLH includes immune-suppressive and immune-modulatory agents, cytostatic drugs, and biological response modifiers. For patients with FHL, stem cell transplantation is indicated and can be curative.
Annual Review of Medicine – Annual Reviews
Published: Feb 18, 2012
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