Frontiers in Immunology (Aug 2023)
Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS)
- Jonas Johannes Papendorf,
- Frédéric Ebstein,
- Sara Alehashemi,
- Daniela Gerent Petry Piotto,
- Anna Kozlova,
- Maria Teresa Terreri,
- Anna Shcherbina,
- Andre Rastegar,
- Marta Rodrigues,
- Renan Pereira,
- Sophia Park,
- Bin Lin,
- Kat Uss,
- Sophie Möller,
- Ana Flávia da Silva Pina,
- Flavio Sztajnbok,
- Sofia Torreggiani,
- Julie Niemela,
- Jennifer Stoddard,
- Sergio D. Rosenzweig,
- Andrew J. Oler,
- Colton McNinch,
- Marietta M. de Guzman,
- Adriana Fonseca,
- Nicole Micheloni,
- Melissa Mariti Fraga,
- Sandro Félix Perazzio,
- Raphaela Goldbach-Mansky,
- Adriana A. de Jesus,
- Elke Krüger
Affiliations
- Jonas Johannes Papendorf
- Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany
- Frédéric Ebstein
- Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany
- Sara Alehashemi
- Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Daniela Gerent Petry Piotto
- Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Anna Kozlova
- Department of Immunology, D.Rogachev National Medical and Research Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russia
- Maria Teresa Terreri
- Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Anna Shcherbina
- Department of Immunology, D.Rogachev National Medical and Research Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russia
- Andre Rastegar
- Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Marta Rodrigues
- Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Renan Pereira
- Department of Pediatrics, Universidade Federal de Ciencias da Saude de Porto Alegre, Porto Alegre, Brazil
- Sophia Park
- Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Bin Lin
- Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Kat Uss
- Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Sophie Möller
- Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany
- Ana Flávia da Silva Pina
- Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Flavio Sztajnbok
- Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Sofia Torreggiani
- Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Julie Niemela
- Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Jennifer Stoddard
- Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Sergio D. Rosenzweig
- Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Andrew J. Oler
- Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Colton McNinch
- Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Marietta M. de Guzman
- Section of Pediatric Rheumatology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, United States
- Adriana Fonseca
- Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Nicole Micheloni
- Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Melissa Mariti Fraga
- Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
- Sandro Félix Perazzio
- 0Division of Rheumatology – Department of Medicine, Universidade Federal de São Paulo (Unifesp), Sao Paulo, Brazil
- Raphaela Goldbach-Mansky
- Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Adriana A. de Jesus
- Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Elke Krüger
- Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany
- DOI
- https://doi.org/10.3389/fimmu.2023.1190104
- Journal volume & issue
-
Vol. 14
Abstract
Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers typically cause recurring autoinflammation referred to as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) or proteasome-associated autoinflammatory syndrome (PRAAS). Patients with CANDLE/PRAAS present with mostly chronically elevated type I interferon scores that emerge as a consequence of increased proteotoxic stress by mechanisms that are not fully understood. Here, we report on five unrelated patients with CANDLE/PRAAS carrying novel inherited proteasome missense and/or nonsense variants. Four patients were compound heterozygous for novel pathogenic variants in the known CANDLE/PRAAS associated genes, PSMB8 and PSMB10, whereas one patient showed additive loss-of-function mutations in PSMB8. Variants in two previously not associated proteasome genes, PSMA5 and PSMC5, were found in a patient who also carried the PSMB8 founder mutation, p.T75M. All newly identified mutations substantially impact the steady-state expression of the affected proteasome subunits and/or their incorporation into mature 26S proteasomes. Our observations expand the spectrum of PRAAS-associated genetic variants and improve a molecular diagnosis and genetic counseling of patients with sterile autoinflammation.
Keywords
- proteasomopathy
- proteasome associated autoinflammatory syndrome
- type I interferon
- interferonopathy
- PSMB8
- PSMB10
