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Immunodeficiency With Susceptibility to Lymphoma With Complex Genotype Affecting Energy Metabolism (Fbp1, Acad9) and Vesicle Trafficking (Rab27a) Publisher Pubmed



Brauer N1 ; Maruta Y2 ; Lisci M3, 4 ; Strege K3 ; Oschlies I5 ; Nakamura H2 ; Bohm S6 ; Lehmberg K6 ; Brandhoff L7 ; Ehl S8 ; Parvaneh N9 ; Klapper W5 ; Fukuda M2 ; Griffiths GM3 Show All Authors
Authors
  1. Brauer N1
  2. Maruta Y2
  3. Lisci M3, 4
  4. Strege K3
  5. Oschlies I5
  6. Nakamura H2
  7. Bohm S6
  8. Lehmberg K6
  9. Brandhoff L7
  10. Ehl S8
  11. Parvaneh N9
  12. Klapper W5
  13. Fukuda M2
  14. Griffiths GM3
  15. Hennies HC7, 10
  16. Niehues T1
  17. Ammann S3, 8
Show Affiliations
Authors Affiliations
  1. 1. Department of Pediatrics, Helios Klinikum, Krefeld, Germany
  2. 2. Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan
  3. 3. Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
  4. 4. Department of Immunobiology, University of Lausanne, Epalinges, Switzerland
  5. 5. Department of Pathology, Haematopathology Section and Lymph Node Registry, University Hospitals Schleswig-Holstein, Christian-Albrecht University, Kiel, Germany
  6. 6. Division of Pediatric Stem Cell Transplantation and Immunology, Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
  7. 7. Cologne Center for Genomics, University Hospital Cologne, Cologne, Germany
  8. 8. Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  9. 9. Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Department of Biological and Geographical Sciences, University of Huddersfield, Huddersfield, United Kingdom

Source: Frontiers in Immunology Published:2023


Abstract

Introduction: Inborn errors of immunity (IEI) are characterized by a dysfunction of the immune system leading to increased susceptibility to infections, impaired immune regulation and cancer. We present a unique consanguineous family with a history of Hodgkin lymphoma, impaired EBV control and a late onset hemophagocytic lymphohistiocytosis (HLH). Methods and results: Overall, family members presented with variable impairment of NK cell and cytotoxic T cell degranulation and cytotoxicity. Exome sequencing identified homozygous variants in RAB27A, FBP1 (Fructose-1,6-bisphosphatase 1) and ACAD9 (Acyl-CoA dehydrogenase family member 9). Variants in RAB27A lead to Griscelli syndrome type 2, hypopigmentation and HLH predisposition. Discussion: Lymphoma is frequently seen in patients with hypomorphic mutations of genes predisposing to HLH. We hypothesize that the variants in FBP1 and ACAD9 might aggravate the clinical and immune phenotype, influence serial killing and lytic granule polarization by CD8 T cells. Understanding of the interplay between the multiple variants identified by whole exome sequencing (WES) is essential for correct interpretation of the immune phenotype and important for critical treatment decisions. Copyright © 2023 Brauer, Maruta, Lisci, Strege, Oschlies, Nakamura, Bohm, Lehmberg, Brandhoff, Ehl, Parvaneh, Klapper, Fukuda, Griffiths, Hennies, Niehues and Ammann.
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