Autophagy-associated immune dysregulation and hyperplasia in a patient with compound heterozygous mutations in ATG9A

Guowu Hu; Pia J Hauk; Nannan Zhang; Waleed Elsegeiny; Carlos M Guardia; Amy Kullas; Kevin Crosby; Robin R Deterding; Michaela Schedel; Paul Reynolds; Jordan K Abbott; Vijaya Knight; Stefania Pittaluga; Mark Raffeld; Sergio D Rosenzweig; Juan S Bonifacino; Gulbu Uzel; Peter R Williamson; Erwin W Gelfand

doi:10.1080/15548627.2022.2093028

Autophagy-associated immune dysregulation and hyperplasia in a patient with compound heterozygous mutations in ATG9A

Autophagy. 2023 Feb;19(2):678-691. doi: 10.1080/15548627.2022.2093028. Epub 2022 Jul 15.

Authors

Guowu Hu^{1

2}, Pia J Hauk^{3

4}, Nannan Zhang¹, Waleed Elsegeiny¹, Carlos M Guardia⁵, Amy Kullas¹, Kevin Crosby¹, Robin R Deterding⁶, Michaela Schedel^{3

7

8}, Paul Reynolds³, Jordan K Abbott^{3

4}, Vijaya Knight⁴, Stefania Pittaluga², Mark Raffeld⁹, Sergio D Rosenzweig⁹, Juan S Bonifacino⁵, Gulbu Uzel¹, Peter R Williamson¹, Erwin W Gelfand³

Affiliations

¹ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
² Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³ Divisions of Allergy and Immunology and Cell Biology and Immunodeficiency Diagnosis and Treatment Program, Department of Pediatrics, National Jewish Health, Denver, CO, USA.
⁴ Section Pediatric Allergy and Immunology, Children's Hospital, Colorado, Aurora, CO, USA.
⁵ Section on Intracellular Protein Trafficking, Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
⁶ Section Pediatric Pulmonary Medicine, Children's Hospital, Colorado, Aurora, CO, USA.
⁷ Department of Pulmonary Medicine, University Medicine Essen-Ruhrlandklinik, Essen, Germany.
⁸ Department of Pulmonary Medicine, University Medicine Essen, University Hospital, Essen, Germany.
⁹ Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, USA.

Abstract

BCL2: BCL2 apoptosis regulator; BCL10: BCL10 immune signaling adaptor; CARD11: caspase recruitment domain family member 11; CBM: CARD11-BCL10-MALT1; CR2: complement C3d receptor 2; EBNA: Epstein Barr nuclear antigen; EBV: Epstein-Barr virus; FCGR3A; Fc gamma receptor IIIa; GLILD: granulomatous-lymphocytic interstitial lung disease; HV: healthy volunteer; IKBKB/IKB kinase: inhibitor of nuclear factor kappa B kinase subunit beta; IL2RA: interleukin 2 receptor subunit alpha; MALT1: MALT1 paracaspase; MS4A1: membrane spanning 4-domain A1; MTOR: mechanistic target of rapamycin kinase; MYC: MYC proto-oncogene, bHLH: transcription factor; NCAM1: neural cell adhesion molecule 1; NFKB: nuclear factor kappa B; NIAID: National Institute of Allergy and Infectious Diseases; NK: natural killer; PTPRC: protein tyrosine phosphatase receptor type C; SELL: selectin L; PBMCs: peripheral blood mononuclear cells; TR: T cell receptor; Tregs: regulatory T cells; WT: wild-type.

Keywords: ATG9A; MTOR; NFKB; T-cell signaling; cellular proliferation; rapamycin.

Publication types

Case Reports
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Autophagy
Autophagy-Related Proteins / genetics
Epstein-Barr Virus Infections*
Herpesvirus 4, Human
Humans
Hyperplasia
Leukocytes, Mononuclear / metabolism
Membrane Proteins / genetics
Mutation
NF-kappa B / metabolism
Proto-Oncogene Proteins c-bcl-2 / genetics
Vesicular Transport Proteins / genetics

Substances

ATG9A protein, human
Autophagy-Related Proteins
Membrane Proteins
NF-kappa B
Proto-Oncogene Proteins c-bcl-2
Vesicular Transport Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding