JOURNAL ARTICLE

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 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 Parvaneh, Nima Rezaei, Geneviève de Saint Basile, Annette Schmitt-Graeff, Klaus Schwarz, Gulsun T Karasu, Barbara Zieger, Udo Zur Stadt, Peter Aichele, Stephan Ehl
Blood 2013 April 11, 121 (15): 2943-51
23403622
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 a moderate defect in CTL cytotoxicity in vivo. However, in contrast to perforin-deficient mice, 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 22 HPS2 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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
23403622
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"