Evaluation of purified natural killer cell functions in familial hemophagocytic lymphohistiocytosis
Abstract
Background: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, genetic, immune dysregulation disorder of aberrant hyperactivation of lymphocytes causing inflammation and hemophagocytosis. We report on a 3-month old male who was evaluated for the possibility of FHL because of a positive family history. The patient was asymptomatic; however, levels of the soluble interleukin 2 (IL-2) receptor were elevated and the quantity and function of the natural killer (NK) cells were severely decreased.
Methods: Purification of NK cells and evaluation of the cytotoxicity and IFNγ/TNFα secretion of NK cells after IL-2 activation relative to the patient's family members.
Results: The patient's NK specific lysis was enhanced compared with his mother, and it was slightly higher than his sister. The IFNγ and TNFα secretion by the patient's NK cells after challenge with target 721 cells or anti-natural cytotoxicity receptors (NKp30 and NKp44) antibodies showed levels that are close to the mother's and sister's NK secretion levels. Owing to a low yield of NK cells from the patient's father the results for his NK cells are incomplete. The patient did not undergo HSCT and continued to be followed. He is now 7 years old and thriving without signs of FHL. His last examination was in August 2012 for functionality of isolated NK cells. The results showed normal cytotoxicity, cytokine secretion, and CD107a up-regulation to the NK cell surface.
Conclusion: We propose that NK function assessment in patients with presumed FHL should be performed on isolated NK cell populations. This practice may reduce the number of false-negative results in NK function assays.
Statement of novelty: In this case report we show that functional assessment of unpurified NK cells could lead to a false-negative assessment in 1 of the parameters in FHL. Assessment of NK function without NK purification may lead to an erroneous diagnosis of poor NK function.
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REFERENCES
Aricò M., Janka G., Fischer A., Henter J.I., Blanche S., Elinder G., Martinetti M., and Rusca M.P. Hemophagocytic lymphohistiocytosis Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. Leukemia 1996 10 2 197 -203
Fisman D.N. Hemophagocytic syndromes and infection Emerg. Infect. Dis 2000 6 6 601 -608
Gholam C., Grigoriadou S., Gilmour K.C., and Gaspar H.B. Familial haemophagocytic lymphohistiocytosis: Advances in the genetic basis, diagnosis and management Clin. Exp. Immunol 2011 163 3 271 -283
Hafsteinsdóttir S., Jónmundsson G.K., Kristinsson J., Winiarski J., Henter J.I., and Haraldsson A. Findings in familial haemophagocytic lymphohistiocytosis prior to symptomatic presentation Acta Paediatr 2002 91 8 974 -977
Henter J.-I., Aricò M., Elinder G., Imashuku S., and Janka G. Familial hemophagocytic lymphohistiocytosis. Primary hemophagocytic lymphohistiocytosis Hematol. Oncol. Clin. North. Am 1998 12 2 417 -433
Henter J.-I., Elinder G., Söder O., Hansson M., Andersson B., and Andersson U. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis Blood 1991 78 11 2918 -2922
Henter J.-I., Horne A., Aricó M., Egeler R.M., Filipovich A.H., Imashuku S., Ladisch S., McClain K., Webb D., Winiarski J., and Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007 48 2 124 -131
Henter J.I., Samuelsson-Horne A., Aricò M., Egeler R.M., Elinder G., Filipovich A.H., Gadner H., Imashuku S., Komp D., Ladisch S., Webb D., Janka G., and Histocyte Society Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation Blood 2002 100 7 2367 -2373
Hershkovitz O., Rosental B., Rosenberg L.A., Navarro-Sanchez M.E., Jivov S., Zilka A., Gershoni-Yahalom O., Brient-Litzler E., Bedouelle H., Ho J.W., Campbell K.S., Rager-Zisman B., Despres P., and Porgador A. NKp44 receptor mediates interaction of the envelope glycoproteins from the West Nile and dengue viruses with NK cells J. Immunol 2009 183 4 2610 -2621
Imashuku S. Advances in the management of hemophagocytic lymphohistiocytosis Int. J. Hematol 2000 72 1 1 -11
Janka G.E. Familial and acquired hemophagocytic lymphohistiocytosis Eur. J. Pediatr 2007 166 2 95 -109
Janka G.E. and Schneider E.M. Modern management of children with haemophagocytic lymphohistiocytosis Br. J. Haematol 2004 124 1 4 -14
Jordan M.B., Hildeman D., Kappler J., and Marrack P. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder Blood 2004 104 3 735 -743
Lee S.M., Villanueva J., Sumegi J., Zhang K., Kogawa K., Davis J., and Filipovich A.H. Characterisation of diverse PRF1 mutations leading to decreased natural killer cell activity in North American families with haemophagocytic lymphohistiocytosis J. Med. Genet 2004 41 2 137 -144
Le Garff-Tavernier M., Béziat V., Decocq J., Siguret V., Gandjbakhch F., Pautas E., Debré P., Merle-Beral H., and Vieillard V. Human NK cells display major phenotypic and functional changes over the life span Aging Cell 2010 9 4 527 -535
Ouachée-Chardin M., Elie C., De Saint Basile G., Le Deist F., Mahlaoui N., Picard C., Neven B., Casanova J.L., Tardieu M., Cavazzana-Calvo M., Blanche S., and Fischer A. Hematopoietic stem cell transplantation in hemophagocytic lymphohistiocytosis: A single-center report of 48 patients Pediatrics 2006 117 4 e743 -e750
Rohr J., Beutel K., Maul-Pavicic A., Vraetz T., Thiel J., Warnatz K., Bondzio I., Gross-Wieltsch U., Schündeln M., Schütz B., Woessmann W., Groll A.H., Strahm B., Pagel J., Speckmann C., Janka G., Griffiths G., Schwarz K., zur Stadt U., and Ehl S. Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases Haematologica 2010 95 12 2080 -2087
Rosental B., Brusilovsky M., Hadad U., Oz D., Appel M.Y., Afergan F., Yossef R., Rosenberg L.A., Aharoni A., Cerwenka A., Campbell K.S., Braiman A., and Porgador A. Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44 J. Immunol 2011 187 11 5693 -5702
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Published In
LymphoSign Journal
Volume 2 • Number 4 • December 2015
Pages: 207 - 212
History
Received: 9 July 2015
Accepted: 26 August 2015
Accepted manuscript online: 27 August 2015
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Benyamin Rosental, Shemesh Avishai, Yaron-Mendelson Michal, Klein Lauren C., Kodman Yona, Levy Jacov, Porgador Angel, and Broides Arnon. 2015. Evaluation of purified natural killer cell functions in familial hemophagocytic lymphohistiocytosis. LymphoSign Journal.
2(4): 207-212. https://doi.org/10.14785/lpsn-2015-0007
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