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Kostmann’s Disease and HCLS1-Associated Protein X-1 (HAX1)

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Abstract

Severe congenital neutropenia (SCN), originally described by the Swedish pediatrician Rolf Kostmann, constitutes a heterogeneous disorder associated with a dramatic decrease of peripheral neutrophil granulocytes. Patients suffer from life-threatening bacterial infections unless treated by recombinant human granulocyte colony stimulating factor (G-CSF) or allogeneic hematopoietic stem cells. This review is focused on the SCN variant caused by mutations in HCLS1 Associated Protein X-1 (HAX1) (SCN3, “Kostmann Disease”). HAX1 is a ubiquitously expressed protein with pleotropic functions, including control of cellular viability, migration, and cancer progression. Even though scientific evidence on the molecular mechanisms regarding HAX1 accumulates, no unified picture has emerged. This review highlights historical milestones and our current understanding of SCN related to mutations in HAX1.

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Acknowledgements

I am grateful to many past and present members of my laboratory who dedicated their talent and enthusiasm in an effort to understand the molecular pathophysiology of congenital neutropenia; without their commitment, many of the cited studies could not have been done. I apologize to those researchers whose interesting and valuable scientific contributions could not be cited and commented due to space constraints.

I am grateful to many friends and colleagues all over the world who have been great collaborators over many years, from the international SCN registry to the global Care-for-Rare Alliance. I am grateful to Dr. Göran Carlsson for sharing the original photograph of Dr. Kostmann. This paper has been in part enabled by funds from the European Research Council (ERC Explore), DFG, and the BMBF (DZIF, PIDNET). I thank Yanxin Fan for help regarding figures and Natalia Zietara, Marcin Lyszkiewicz, and Henrike Klinker for their critical reviews.

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  1. Department of Pediatrics, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337, Munich, Germany

    Christoph Klein

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Correspondence to Christoph Klein.

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Klein, C. Kostmann’s Disease and HCLS1-Associated Protein X-1 (HAX1). J Clin Immunol 37, 117–122 (2017). https://doi.org/10.1007/s10875-016-0358-2

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