The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2

Birthe Jessen, Sebastian F N Bode, Sandra Ammann, Subarna Chakravorty, Graham Davies, Jana Diestelhorst, Melissa J Frei-jones, William A. Gahl, Bernadette R. Gochuico, Matthias Griese, Gillian Griffiths, Gritta Janka, Christoph Klein, Tamara Kögl, Karin Kurnik, Kai Lehmberg, Andrea Maul-Pavicic, Andrew D. Mumford, David Pace, Nima ParvanehNima Rezaei, Geneviève De Saint Basile, Annette Schmitt-Graeff, Klaus Schwarz, Gulsun T. Karasu, Barbara Zieger, Udo Zur Stadt, Peter Aichele, Stephan Ehl

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Abstract

Genetic disorders of lymphocyte cytotoxicity predispose patients to hemophagocytic lymphohistiocytosis (HLH). Reduced lymphocyte cytotoxicity has been demonstrated in Hermansky-Pudlak syndrome type 2 (HPS2), but only a single patient was reported who developed HLH. Because that patient also carried a potentially contributing heterozygous RAB27A mutation, the risk for HLH in HPS2 remains unclear. We analyzed susceptibility to HLH in the pearl mouse model of HPS2. After infection with lymphocytic choriomeningitis virus, pearl mice developed all key features of HLH, linked to impaired virus control caused by amoderate defect in CTL cytotoxicity in vivo. However, in contrast to perforin-deficientmice, the disease was transient, and all mice fully recovered and controlled the infection. An additional heterozygous Rab27a mutation did not aggravate the cytotoxicity defect or disease parameters. In the largest survey of 22HPS2 patients covering 234 patient years, we identified only 1 additional patient with HLH and 2 with incomplete transient HLH-like episodes, although cytotoxicity or degranulation was impaired in all 16 patients tested. HPS2 confers a risk for HLH that is lower than in Griscelli or Chediak-Higashi syndrome, probably because of a milder defect in cytotoxicity. Preemptive hematopoietic stem cell transplantation does not appear justified in HPS2.

Original languageEnglish (US)
Pages (from-to)2943-2951
Number of pages9
JournalBlood
Volume121
Issue number15
DOIs
StatePublished - Apr 11 2013

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Hemophagocytic Lymphohistiocytosis
Cytotoxicity
Lymphocytes
Viruses
Defects
Perforin
Chediak-Higashi Syndrome
Lymphocytic choriomeningitis virus
Stem cells
Mutation
Inborn Genetic Diseases
Hermansky Pudlak syndrome 2
Hematopoietic Stem Cell Transplantation
Infection

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Jessen, B., Bode, S. F. N., Ammann, S., Chakravorty, S., Davies, G., Diestelhorst, J., ... Ehl, S. (2013). The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2. Blood, 121(15), 2943-2951. https://doi.org/10.1182/blood-2012-10-463166

The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2. / Jessen, Birthe; Bode, Sebastian F N; Ammann, Sandra; Chakravorty, Subarna; Davies, Graham; Diestelhorst, Jana; Frei-jones, Melissa J; Gahl, William A.; Gochuico, Bernadette R.; Griese, Matthias; Griffiths, Gillian; Janka, Gritta; Klein, Christoph; Kögl, Tamara; Kurnik, Karin; Lehmberg, Kai; Maul-Pavicic, Andrea; Mumford, Andrew D.; Pace, David; Parvaneh, Nima; Rezaei, Nima; De Saint Basile, Geneviève; Schmitt-Graeff, Annette; Schwarz, Klaus; Karasu, Gulsun T.; Zieger, Barbara; Zur Stadt, Udo; Aichele, Peter; Ehl, Stephan.

In: Blood, Vol. 121, No. 15, 11.04.2013, p. 2943-2951.

Research output: Contribution to journalArticle

Jessen, B, Bode, SFN, Ammann, S, Chakravorty, S, Davies, G, Diestelhorst, J, Frei-jones, MJ, Gahl, WA, Gochuico, BR, Griese, M, Griffiths, G, Janka, G, Klein, C, Kögl, T, Kurnik, K, Lehmberg, K, Maul-Pavicic, A, Mumford, AD, Pace, D, Parvaneh, N, Rezaei, N, De Saint Basile, G, Schmitt-Graeff, A, Schwarz, K, Karasu, GT, Zieger, B, Zur Stadt, U, Aichele, P & Ehl, S 2013, 'The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2', Blood, vol. 121, no. 15, pp. 2943-2951. https://doi.org/10.1182/blood-2012-10-463166
Jessen B, Bode SFN, Ammann S, Chakravorty S, Davies G, Diestelhorst J et al. The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2. Blood. 2013 Apr 11;121(15):2943-2951. https://doi.org/10.1182/blood-2012-10-463166
Jessen, Birthe ; Bode, Sebastian F N ; Ammann, Sandra ; Chakravorty, Subarna ; Davies, Graham ; Diestelhorst, Jana ; Frei-jones, Melissa J ; Gahl, William A. ; Gochuico, Bernadette R. ; Griese, Matthias ; Griffiths, Gillian ; Janka, Gritta ; Klein, Christoph ; Kögl, Tamara ; Kurnik, Karin ; Lehmberg, Kai ; Maul-Pavicic, Andrea ; Mumford, Andrew D. ; Pace, David ; Parvaneh, Nima ; Rezaei, Nima ; De Saint Basile, Geneviève ; Schmitt-Graeff, Annette ; Schwarz, Klaus ; Karasu, Gulsun T. ; Zieger, Barbara ; Zur Stadt, Udo ; Aichele, Peter ; Ehl, Stephan. / The risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2. In: Blood. 2013 ; Vol. 121, No. 15. pp. 2943-2951.
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AU - Davies, Graham

AU - Diestelhorst, Jana

AU - Frei-jones, Melissa J

AU - Gahl, William A.

AU - Gochuico, Bernadette R.

AU - Griese, Matthias

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AU - Janka, Gritta

AU - Klein, Christoph

AU - Kögl, Tamara

AU - Kurnik, Karin

AU - Lehmberg, Kai

AU - Maul-Pavicic, Andrea

AU - Mumford, Andrew D.

AU - Pace, David

AU - Parvaneh, Nima

AU - Rezaei, Nima

AU - De Saint Basile, Geneviève

AU - Schmitt-Graeff, Annette

AU - Schwarz, Klaus

AU - Karasu, Gulsun T.

AU - Zieger, Barbara

AU - Zur Stadt, Udo

AU - Aichele, Peter

AU - Ehl, Stephan

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