Immunodeficiency with susceptibility to lymphoma with complex genotype affecting energy metabolism ( FBP1, ACAD9) and vesicle trafficking (RAB27A) .

Autor:	Brauer N; Department of Pediatrics, Helios Klinikum, Krefeld, Germany., Maruta Y; Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan., Lisci M; Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.; Department of Immunobiology, University of Lausanne, Epalinges, Switzerland., Strege K; Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom., Oschlies I; Department of Pathology, Haematopathology Section and Lymph Node Registry, University Hospitals Schleswig-Holstein, Christian-Albrecht University, Kiel, Germany., Nakamura H; Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan., Böhm S; Division of Pediatric Stem Cell Transplantation and Immunology, Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany., Lehmberg K; Division of Pediatric Stem Cell Transplantation and Immunology, Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany., Brandhoff L; Cologne Center for Genomics, University Hospital Cologne, Cologne, Germany., Ehl S; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Parvaneh N; Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran., Klapper W; Department of Pathology, Haematopathology Section and Lymph Node Registry, University Hospitals Schleswig-Holstein, Christian-Albrecht University, Kiel, Germany., Fukuda M; Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan., Griffiths GM; Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom., Hennies HC; Cologne Center for Genomics, University Hospital Cologne, Cologne, Germany.; Department of Biological and Geographical Sciences, University of Huddersfield, Huddersfield, United Kingdom., Niehues T; Department of Pediatrics, Helios Klinikum, Krefeld, Germany., Ammann S; Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jun 14; Vol. 14, pp. 1151166. Date of Electronic Publication: 2023 Jun 14 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1151166
Abstrakt:	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. Competing Interests: KS is an employee of AstraZeneca and has stock ownership and/or stock options or interests in the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Brauer, Maruta, Lisci, Strege, Oschlies, Nakamura, Böhm, Lehmberg, Brandhoff, Ehl, Parvaneh, Klapper, Fukuda, Griffiths, Hennies, Niehues and Ammann.)
Databáze:	MEDLINE
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