Gain-of-function CEBPE mutation causes noncanonical autoinflammatory inflammasomopathy
CCAAT enhancer–binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil...
Saved in:
| Published in | Journal of allergy and clinical immunology Vol. 144; no. 5; pp. 1364 - 1376 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.11.2019
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | CCAAT enhancer–binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil function and early mortality.
The aim of this study was to molecularly characterize the effects of C/EBPε transcription factor Arg219His mutation identified in a Finnish family with previously genetically uncharacterized autoinflammatory and immunodeficiency syndrome.
Genetic analysis, proteomics, genome-wide transcriptional profiling by means of RNA-sequencing, chromatin immunoprecipitation (ChIP) sequencing, and assessment of the inflammasome function of primary macrophages were performed.
Studies revealed a novel mechanism of genome-wide gain-of-function that dysregulated transcription of 464 genes. Mechanisms involved dysregulated noncanonical inflammasome activation caused by decreased association with transcriptional repressors, leading to increased chromatin occupancy and considerable changes in transcriptional activity, including increased expression of NLR family, pyrin domain-containing 3 protein (NLRP3) and constitutively expressed caspase-5 in macrophages.
We describe a novel autoinflammatory disease with defective neutrophil function caused by a homozygous Arg219His mutation in the transcription factor C/EBPε. Mutated C/EBPε acts as a regulator of both the inflammasome and interferome, and the Arg219His mutation causes the first human monogenic neomorphic and noncanonical inflammasomopathy/immunodeficiency. The mechanism, including widely dysregulated transcription, is likely not unique for C/EBPε. Similar multiomics approaches should also be used in studying other transcription factor–associated diseases.
[Display omitted] |
|---|---|
| AbstractList | CCAAT enhancer–binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil function and early mortality.
The aim of this study was to molecularly characterize the effects of C/EBPε transcription factor Arg219His mutation identified in a Finnish family with previously genetically uncharacterized autoinflammatory and immunodeficiency syndrome.
Genetic analysis, proteomics, genome-wide transcriptional profiling by means of RNA-sequencing, chromatin immunoprecipitation (ChIP) sequencing, and assessment of the inflammasome function of primary macrophages were performed.
Studies revealed a novel mechanism of genome-wide gain-of-function that dysregulated transcription of 464 genes. Mechanisms involved dysregulated noncanonical inflammasome activation caused by decreased association with transcriptional repressors, leading to increased chromatin occupancy and considerable changes in transcriptional activity, including increased expression of NLR family, pyrin domain-containing 3 protein (NLRP3) and constitutively expressed caspase-5 in macrophages.
We describe a novel autoinflammatory disease with defective neutrophil function caused by a homozygous Arg219His mutation in the transcription factor C/EBPε. Mutated C/EBPε acts as a regulator of both the inflammasome and interferome, and the Arg219His mutation causes the first human monogenic neomorphic and noncanonical inflammasomopathy/immunodeficiency. The mechanism, including widely dysregulated transcription, is likely not unique for C/EBPε. Similar multiomics approaches should also be used in studying other transcription factor–associated diseases.
[Display omitted] BackgroundCCAAT enhancer–binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil function and early mortality.ObjectiveThe aim of this study was to molecularly characterize the effects of C/EBPε transcription factor Arg219His mutation identified in a Finnish family with previously genetically uncharacterized autoinflammatory and immunodeficiency syndrome.MethodsGenetic analysis, proteomics, genome-wide transcriptional profiling by means of RNA-sequencing, chromatin immunoprecipitation (ChIP) sequencing, and assessment of the inflammasome function of primary macrophages were performed.ResultsStudies revealed a novel mechanism of genome-wide gain-of-function that dysregulated transcription of 464 genes. Mechanisms involved dysregulated noncanonical inflammasome activation caused by decreased association with transcriptional repressors, leading to increased chromatin occupancy and considerable changes in transcriptional activity, including increased expression of NLR family, pyrin domain-containing 3 protein (NLRP3) and constitutively expressed caspase-5 in macrophages.ConclusionWe describe a novel autoinflammatory disease with defective neutrophil function caused by a homozygous Arg219His mutation in the transcription factor C/EBPε. Mutated C/EBPε acts as a regulator of both the inflammasome and interferome, and the Arg219His mutation causes the first human monogenic neomorphic and noncanonical inflammasomopathy/immunodeficiency. The mechanism, including widely dysregulated transcription, is likely not unique for C/EBPε. Similar multiomics approaches should also be used in studying other transcription factor–associated diseases. CCAAT enhancer-binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil function and early mortality.BACKGROUNDCCAAT enhancer-binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil function and early mortality.The aim of this study was to molecularly characterize the effects of C/EBPε transcription factor Arg219His mutation identified in a Finnish family with previously genetically uncharacterized autoinflammatory and immunodeficiency syndrome.OBJECTIVEThe aim of this study was to molecularly characterize the effects of C/EBPε transcription factor Arg219His mutation identified in a Finnish family with previously genetically uncharacterized autoinflammatory and immunodeficiency syndrome.Genetic analysis, proteomics, genome-wide transcriptional profiling by means of RNA-sequencing, chromatin immunoprecipitation (ChIP) sequencing, and assessment of the inflammasome function of primary macrophages were performed.METHODSGenetic analysis, proteomics, genome-wide transcriptional profiling by means of RNA-sequencing, chromatin immunoprecipitation (ChIP) sequencing, and assessment of the inflammasome function of primary macrophages were performed.Studies revealed a novel mechanism of genome-wide gain-of-function that dysregulated transcription of 464 genes. Mechanisms involved dysregulated noncanonical inflammasome activation caused by decreased association with transcriptional repressors, leading to increased chromatin occupancy and considerable changes in transcriptional activity, including increased expression of NLR family, pyrin domain-containing 3 protein (NLRP3) and constitutively expressed caspase-5 in macrophages.RESULTSStudies revealed a novel mechanism of genome-wide gain-of-function that dysregulated transcription of 464 genes. Mechanisms involved dysregulated noncanonical inflammasome activation caused by decreased association with transcriptional repressors, leading to increased chromatin occupancy and considerable changes in transcriptional activity, including increased expression of NLR family, pyrin domain-containing 3 protein (NLRP3) and constitutively expressed caspase-5 in macrophages.We describe a novel autoinflammatory disease with defective neutrophil function caused by a homozygous Arg219His mutation in the transcription factor C/EBPε. Mutated C/EBPε acts as a regulator of both the inflammasome and interferome, and the Arg219His mutation causes the first human monogenic neomorphic and noncanonical inflammasomopathy/immunodeficiency. The mechanism, including widely dysregulated transcription, is likely not unique for C/EBPε. Similar multiomics approaches should also be used in studying other transcription factor-associated diseases.CONCLUSIONWe describe a novel autoinflammatory disease with defective neutrophil function caused by a homozygous Arg219His mutation in the transcription factor C/EBPε. Mutated C/EBPε acts as a regulator of both the inflammasome and interferome, and the Arg219His mutation causes the first human monogenic neomorphic and noncanonical inflammasomopathy/immunodeficiency. The mechanism, including widely dysregulated transcription, is likely not unique for C/EBPε. Similar multiomics approaches should also be used in studying other transcription factor-associated diseases. CCAAT enhancer-binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil function and early mortality. The aim of this study was to molecularly characterize the effects of C/EBPε transcription factor Arg219His mutation identified in a Finnish family with previously genetically uncharacterized autoinflammatory and immunodeficiency syndrome. Genetic analysis, proteomics, genome-wide transcriptional profiling by means of RNA-sequencing, chromatin immunoprecipitation (ChIP) sequencing, and assessment of the inflammasome function of primary macrophages were performed. Studies revealed a novel mechanism of genome-wide gain-of-function that dysregulated transcription of 464 genes. Mechanisms involved dysregulated noncanonical inflammasome activation caused by decreased association with transcriptional repressors, leading to increased chromatin occupancy and considerable changes in transcriptional activity, including increased expression of NLR family, pyrin domain-containing 3 protein (NLRP3) and constitutively expressed caspase-5 in macrophages. We describe a novel autoinflammatory disease with defective neutrophil function caused by a homozygous Arg219His mutation in the transcription factor C/EBPε. Mutated C/EBPε acts as a regulator of both the inflammasome and interferome, and the Arg219His mutation causes the first human monogenic neomorphic and noncanonical inflammasomopathy/immunodeficiency. The mechanism, including widely dysregulated transcription, is likely not unique for C/EBPε. Similar multiomics approaches should also be used in studying other transcription factor-associated diseases. |
| Author | Järvinen, Asko Seppänen, Mikko R.J. Vihinen, Helena Greco, Dario Nejentsev, Sergey Plagnol, Vincent Varjosalo, Markku Pettersson, Tom Kovanen, Panu E. Vaarala, Outi Saavalainen, Päivi Kere, Juha Fogarty, Christopher L. Eklund, Kari K. Sahu, Biswajyoti Einarsdottir, Elisabet Scala, Giovanni Nurmi, Katariina Keskitalo, Salla Notarangelo, Luigi D. Ranki, Annamari Liu, Xiaonan Lehto, Markku Krjutskov, Kaarel Curtis, James Taipale, Jussi Jouppila, Annukka Muurinen, Mari Flaumenhaft, Robert Göös, Helka Nordström, Dan Rajamäki, Kristiina |
| AuthorAffiliation | i Folkhälsan Institute of Genetics, Helsinki k Research Programs Unit, Molecular Neurology, University of Helsinki q Department of Medical and Clinical Genetics, University of Helsinki d Diabetes & Obesity Research Program, Research Program’s Unit, University of Helsinki r Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital ff Rare Diseases Center and Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital ee Department of Biochemistry, Cambridge University x Respiratory, Inflammation and Autoimmunity, Innovative Medicine, AstraZeneca, Mölndal s Faculty of Medicine and Life Sciences & Institute of Biosciences and Medical Technology, University of Tampere dd Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna c Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital w |
| AuthorAffiliation_xml | – name: y Department of Pathology, University of Helsinki, and HUSLAB, Helsinki University Hospital – name: ff Rare Diseases Center and Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital – name: p Research Programs Unit, Immunobiology, University of Helsinki – name: x Respiratory, Inflammation and Autoimmunity, Innovative Medicine, AstraZeneca, Mölndal – name: j Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm – name: b Folkhälsan Research Center, Helsinki – name: ee Department of Biochemistry, Cambridge University – name: d Diabetes & Obesity Research Program, Research Program’s Unit, University of Helsinki – name: aa School of Basic and Medical Biosciences, King’s College London, Guy’s Hospital, London – name: m Department of Internal Medicine and Rehabilitation, Helsinki University Hospital, Helsinki – name: cc Orton Orthopaedic Hospital and Research Institute, Invalid Foundation, Helsinki – name: e Institute of Clinical Medicine, University of Helsinki – name: t Department of Medicine, University of Cambridge – name: z Department of Dermatology, Allergology and Venereal Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital – name: f Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki – name: k Research Programs Unit, Molecular Neurology, University of Helsinki – name: i Folkhälsan Institute of Genetics, Helsinki – name: c Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital – name: q Department of Medical and Clinical Genetics, University of Helsinki – name: o Competence Centre on Health Technologies, Tartu – name: u Department of Rheumatology, Inflammation Center, University of Helsinki and Helsinki University Hospital – name: g University College London Genetics Institute, University College London – name: bb Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda – name: dd Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna – name: r Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital – name: w Pediatric Research Center, University of Helsinki and Helsinki University Hospital – name: h Clinicum, Faculty of Medicine, University of Helsinki – name: n Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki – name: s Faculty of Medicine and Life Sciences & Institute of Biosciences and Medical Technology, University of Tampere – name: v Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston – name: l Helsinki University Hospital Research Institute – name: a Institute of Biotechnology, HiLIFE, University of Helsinki |
| Author_xml | – sequence: 1 givenname: Helka surname: Göös fullname: Göös, Helka organization: Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland – sequence: 2 givenname: Christopher L. surname: Fogarty fullname: Fogarty, Christopher L. organization: Folkhälsan Research Center, Helsinki, Finland – sequence: 3 givenname: Biswajyoti surname: Sahu fullname: Sahu, Biswajyoti organization: Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland – sequence: 4 givenname: Vincent surname: Plagnol fullname: Plagnol, Vincent organization: University College London Genetics Institute, University College London, London, United Kingdom – sequence: 5 givenname: Kristiina surname: Rajamäki fullname: Rajamäki, Kristiina organization: Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland – sequence: 6 givenname: Katariina surname: Nurmi fullname: Nurmi, Katariina organization: Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland – sequence: 7 givenname: Xiaonan surname: Liu fullname: Liu, Xiaonan organization: Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland – sequence: 8 givenname: Elisabet surname: Einarsdottir fullname: Einarsdottir, Elisabet organization: Folkhälsan Institute of Genetics, Helsinki, Finland – sequence: 9 givenname: Annukka surname: Jouppila fullname: Jouppila, Annukka organization: Helsinki University Hospital Research Institute, Helsinki, Finland – sequence: 10 givenname: Tom surname: Pettersson fullname: Pettersson, Tom organization: Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland – sequence: 11 givenname: Helena surname: Vihinen fullname: Vihinen, Helena organization: Electron Microscopy Unit, Institute of Biotechnology, University of Helsinki, Helsinki, Finland – sequence: 12 givenname: Kaarel surname: Krjutskov fullname: Krjutskov, Kaarel organization: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden – sequence: 13 givenname: Päivi surname: Saavalainen fullname: Saavalainen, Päivi organization: Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland – sequence: 14 givenname: Asko surname: Järvinen fullname: Järvinen, Asko organization: Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland – sequence: 15 givenname: Mari surname: Muurinen fullname: Muurinen, Mari organization: Folkhälsan Institute of Genetics, Helsinki, Finland – sequence: 16 givenname: Dario surname: Greco fullname: Greco, Dario organization: Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland – sequence: 17 givenname: Giovanni surname: Scala fullname: Scala, Giovanni organization: Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland – sequence: 18 givenname: James surname: Curtis fullname: Curtis, James organization: Department of Medicine, University of Cambridge, Cambridge, United Kingdom – sequence: 19 givenname: Dan surname: Nordström fullname: Nordström, Dan organization: Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland – sequence: 20 givenname: Robert surname: Flaumenhaft fullname: Flaumenhaft, Robert organization: Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, Mass – sequence: 21 givenname: Outi surname: Vaarala fullname: Vaarala, Outi organization: Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland – sequence: 22 givenname: Panu E. surname: Kovanen fullname: Kovanen, Panu E. organization: Department of Pathology, University of Helsinki, and HUSLAB, Helsinki University Hospital, Helsinki, Finland – sequence: 23 givenname: Salla surname: Keskitalo fullname: Keskitalo, Salla organization: Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland – sequence: 24 givenname: Annamari surname: Ranki fullname: Ranki, Annamari organization: Department of Dermatology, Allergology and Venereal Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland – sequence: 25 givenname: Juha surname: Kere fullname: Kere, Juha organization: Folkhälsan Institute of Genetics, Helsinki, Finland – sequence: 26 givenname: Markku surname: Lehto fullname: Lehto, Markku organization: Folkhälsan Research Center, Helsinki, Finland – sequence: 27 givenname: Luigi D. surname: Notarangelo fullname: Notarangelo, Luigi D. organization: Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md – sequence: 28 givenname: Sergey surname: Nejentsev fullname: Nejentsev, Sergey organization: Department of Medicine, University of Cambridge, Cambridge, United Kingdom – sequence: 29 givenname: Kari K. surname: Eklund fullname: Eklund, Kari K. organization: Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland – sequence: 30 givenname: Markku surname: Varjosalo fullname: Varjosalo, Markku organization: Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland – sequence: 31 givenname: Jussi surname: Taipale fullname: Taipale, Jussi organization: Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland – sequence: 32 givenname: Mikko R.J. surname: Seppänen fullname: Seppänen, Mikko R.J. email: mikko.seppanen@hus.fi organization: Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31201888$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:142226366$$DView record from Swedish Publication Index |
| BookMark | eNqFUlFvFCEQJqbGXk__gA9mE1982RXYZQFjYvRyrSZN9EF9JRw7WLa7cC5szf37cr2rsX0xIQPDfN8wzHxn6MQHDwi9JLgimLRv-6rXxlUUE1nhtsK4foIWBEtetoKyE7TAWJKy5Y08RWcx9jj7tZDP0GlNMkkIsUA_L7TzZbClnb1JLvhitf70bV2Mc9J3rtFzhFjkp43Oxhk9FHpOwXk76HHUKUy74t6JYQxbna52z9FTq4cIL477Ev04X39ffS4vv158WX28LIE1PJW2aajoLLNMUKLBUrAb22DLCWu5NKAbRnhHJTO444YyKfPHs4WN6DrWiXqJykPe-Ae280ZtJzfqaaeCdup4dZ1PoBoucUsy_sMBnyMjdAZ8mvTwgPYw4t2V-hVuFCGY8TqvJXpzzDCF3zPEpEYXDQyD9hDmqCjllBJBKcvQ14-gfZgnn_uhaJ5ARnJeZ9Srf0v6W8v9jDLg_QEAuZE3DiYVjQNvoHMTmKS64BTBai8J1au9JNReEgq3Kksi0989opvB3c3xGnb_I98CIe7AUw |
| ContentType | Journal Article |
| Copyright | 2019 The Authors Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved. 2019. The Authors |
| Copyright_xml | – notice: 2019 The Authors – notice: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved. – notice: 2019. The Authors |
| DBID | 6I. AAFTH CGR CUY CVF ECM EIF NPM 7SS 7T5 H94 K9. NAPCQ 7X8 5PM ADTPV AOWAS |
| DOI | 10.1016/j.jaci.2019.06.003 |
| DatabaseName | ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Entomology Abstracts (Full archive) Immunology Abstracts AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Premium MEDLINE - Academic PubMed Central (Full Participant titles) SwePub SwePub Articles |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Entomology Abstracts AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Premium Immunology Abstracts MEDLINE - Academic |
| DatabaseTitleList | Entomology Abstracts MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1097-6825 |
| EndPage | 1376 |
| ExternalDocumentID | oai_swepub_ki_se_479061 PMC11057357 31201888 S0091674919307626 |
| Genre | Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Journal Article Case Reports |
| GeographicLocations | Finland |
| GeographicLocations_xml | – name: Finland |
| GrantInformation_xml | – fundername: Medical Research Council grantid: MR/M012328/2 – fundername: Intramural NIH HHS grantid: Z99 AI999999 |
| GroupedDBID | --- --K --M -~X .1- .55 .FO .GJ .XZ .~1 0R~ 1B1 1P~ 1RT 1~. 1~5 354 3O- 4.4 457 4G. 53G 5GY 5RE 5VS 7-5 71M 8F7 8FE 8FH 8P~ 9JM AAAJQ AABNK AAEDT AAEDW AAFWJ AAIKJ AAKOC AALRI AAOAW AAQFI AAQXK AARKO AATTM AAXKI AAXUO AAYWO ABBQC ABFNM ABJNI ABLJU ABMAC ABMZM ABOCM ABWVN ABXDB ACDAQ ACGFO ACGFS ACIEU ACPRK ACRLP ACRPL ACVFH ADBBV ADCNI ADEZE ADFRT ADMUD ADNMO ADVLN ADXHL AEBSH AEIPS AEKER AENEX AEUPX AFFNX AFJKZ AFPUW AFRAH AFRHN AFTJW AFXIZ AGCQF AGEKW AGHFR AGQPQ AGUBO AGYEJ AHHHB AHMBA AIEXJ AIGII AIIUN AIKHN AITUG AJRQY AJUYK AKBMS AKRWK AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ ANKPU ANZVX APXCP ASPBG AVWKF AXJTR AZFZN BKOJK BLXMC BNPGV BPHCQ BVXVI C45 CAG CJTIS COF CS3 DU5 EBS EFJIC EFKBS EJD EO8 EO9 EP2 EP3 EX3 F5P FDB FEDTE FGOYB FIRID FNPLU FYGXN G-2 G-Q GBLVA HDU HMK HMO HVGLF HZ~ IHE J1W J5H K-O KOM L7B LK8 LUGTX M27 M41 MO0 N4W N9A O-L O9- O9~ OAUVE OBH ODZKP OHH OHT OK0 OK1 OVD OZT P-8 P-9 P2P PC. PQQKQ PROAC Q38 R2- ROL RPZ SAE SCC SDF SDG SDP SEL SES SEW SJN SPCBC SSH SSI SSZ T5K TEORI TWZ UGJ UNMZH UV1 WH7 WOW WUQ X7M XFW YOC YQI YQJ Z5R ZGI ZXP ZY1 ~02 ~G- ~KM 6I. AACTN AAFTH RIG AGRNS CGR CUY CVF ECM EIF NPM 7SS 7T5 H94 K9. NAPCQ 7X8 5PM ADTPV AOWAS |
| ID | FETCH-LOGICAL-e547t-f4428df5f5821aef2efbf40f715679cea4517d295c0d7c2599101599eb8dd5d83 |
| IEDL.DBID | .~1 |
| ISSN | 0091-6749 1097-6825 |
| IngestDate | Mon Aug 25 03:34:27 EDT 2025 Thu Aug 21 18:34:20 EDT 2025 Fri Jul 11 08:33:21 EDT 2025 Wed Aug 13 03:12:11 EDT 2025 Mon Jul 21 06:02:54 EDT 2025 Sun Apr 06 06:53:10 EDT 2025 Tue Aug 26 17:44:35 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 5 |
| Keywords | NLR family C/EBP autoinflammatory diseases PPI Immunologic deficiency syndromes ChIP NF-κB interferons pyrin domain-containing 3 protein RNA-seq FDR NLRP3 AID CAIN WT chemotaxis GOF LOF gain-of-function mutation inflammasomes PID SGD SMRC2 STAT JAK ChIP-seq neomorphic mutation hereditary FC |
| Language | English |
| License | This is an open access article under the CC BY-NC-ND license. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-e547t-f4428df5f5821aef2efbf40f715679cea4517d295c0d7c2599101599eb8dd5d83 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Case Study-2 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 These authors contributed equally to this work. |
| OpenAccessLink | https://www.sciencedirect.com/science/article/pii/S0091674919307626 |
| PMID | 31201888 |
| PQID | 2312227773 |
| PQPubID | 105664 |
| PageCount | 13 |
| ParticipantIDs | swepub_primary_oai_swepub_ki_se_479061 pubmedcentral_primary_oai_pubmedcentral_nih_gov_11057357 proquest_miscellaneous_2272218225 proquest_journals_2312227773 pubmed_primary_31201888 elsevier_sciencedirect_doi_10_1016_j_jaci_2019_06_003 elsevier_clinicalkey_doi_10_1016_j_jaci_2019_06_003 |
| PublicationCentury | 2000 |
| PublicationDate | 2019-11-01 |
| PublicationDateYYYYMMDD | 2019-11-01 |
| PublicationDate_xml | – month: 11 year: 2019 text: 2019-11-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: St. Louis |
| PublicationTitle | Journal of allergy and clinical immunology |
| PublicationTitleAlternate | J Allergy Clin Immunol |
| PublicationYear | 2019 |
| Publisher | Elsevier Inc Elsevier Limited |
| Publisher_xml | – name: Elsevier Inc – name: Elsevier Limited |
| References | Fliegauf, Bryant, Frede, Slade, Woon, Lehnert (bib30) 2015; 97 Pasanen, Ruutu, Kosunen, Tenhunen (bib17) 1987; 39 Guarda, Braun, Staehli, Tardivel, Mattmann, Forster (bib39) 2011; 34 Antonson, Stellan, Yamanaka, Xanthopoulos (bib35) 1996; 35 Bedi, Du, Sharma, Gomes, Ackerman (bib11) 2009; 113 Yamanaka, Barlow, Lekstrom-Himes, Castilla, Liu, Eckhaus (bib15) 1997; 94 Boisson, Quartier, Casanova (bib4) 2015; 32 Lominadze, Powell, Luerman, Link, Ward, McLeish (bib29) 2005; 4 Henry, Brotcke, Weiss, Thompson, Monack (bib40) 2007; 204 Repo, Vuopio, Leirisalo, Jansson, Kosunen (bib18) 1979; 36 Meunier, Dick, Dreier, Schurmann, Kenzelmann Broz, Warming (bib7) 2014; 509 Kerur, Fukuda, Banerjee, Kim, Fu, Apicella (bib10) 2018; 24 Witzel, Petersheim, Fan, Bahrami, Racek, Rohlfs (bib23) 2017; 49 Zhu, Sammons, Donahue, Dou, Vedadi, Getlik (bib25) 2015; 525 Crisford, Sapey, Stockley (bib26) 2018; 19 Lekstrom-Himes (bib21) 2001; 19 Schipp, Nabhani, Bienemann, Simanovsky, Kfir-Erenfeld, Assayag-Asherie (bib32) 2016; 101 Khanna-Gupta, Sun, Zibello, Lee, Dahl, Boxer (bib14) 2007; 109 Toubiana, Okada, Hiller, Oleastro, Lagos Gomez, Aldave Becerra (bib34) 2016; 127 Murros, Konttinen (bib16) 1974; 43 Zamoshnikova, Gross, Schuster, Chen, Wilson, Tacchini-Cottier (bib28) 2016; 221 Picard, Bobby Gaspar, Al-Herz, Bousfiha, Casanova, Chatila (bib2) 2018; 38 Liu, Salokas, Tamene, Jiu, Weldatsadik, Ohman (bib19) 2018; 9 Broz, Ruby, Belhocine, Bouley, Kayagaki, Dixit (bib37) 2012; 490 Yamanaka, Kim, Radomska, Lekstrom-Himes, Smith, Antonson (bib22) 1997; 94 Joosten, Netea, Fantuzzi, Koenders, Helsen, Sparrer (bib27) 2009; 60 Gombart, Shiohara, Kwok, Agematsu, Komiyama, Koeffler (bib12) 2001; 97 Bousfiha, Jeddane, Picard, Ailal, Bobby Gaspar, Al-Herz (bib3) 2018; 38 Gurung, Malireddi, Anand, Demon, Vande Walle, Liu (bib6) 2012; 287 Pellegrini, Antonioli, Lopez-Castejon, Blandizzi, Fornai (bib36) 2017; 8 Schauvliege, Vanrobaeys, Schotte, Beyaert (bib9) 2002; 277 Serwas, Huemer, Dieckmann, Mejstrikova, Garncarz, Litzman (bib24) 2018; 9 Crow, Manel (bib38) 2015; 15 Rathinam, Vanaja, Waggoner, Sokolovska, Becker, Stuart (bib8) 2012; 150 Kulkarni (bib20) 2011 Vodovotz, Csete, Bartels, Chang, An (bib1) 2008; 4 Lekstrom-Himes, Xanthopoulos (bib13) 1999; 93 Kaustio, Haapaniemi, Goos, Hautala, Park, Syrjanen (bib31) 2017; 140 Lillie, Conn (bib33) 1969 Man, Kanneganti (bib5) 2016; 16 |
| References_xml | – volume: 277 start-page: 41624 year: 2002 end-page: 41630 ident: bib9 article-title: Caspase-11 gene expression in response to lipopolysaccharide and interferon-gamma requires nuclear factor-kappa B and signal transducer and activator of transcription (STAT) 1 publication-title: J Biol Chem – volume: 109 start-page: 4181 year: 2007 end-page: 4190 ident: bib14 article-title: Growth factor independence-1 (Gfi-1) plays a role in mediating specific granule deficiency (SGD) in a patient lacking a gene-inactivating mutation in the C/EBPepsilon gene publication-title: Blood – volume: 204 start-page: 987 year: 2007 end-page: 994 ident: bib40 article-title: Type I interferon signaling is required for activation of the inflammasome during Francisella infection publication-title: J Exp Med – volume: 38 start-page: 96 year: 2018 end-page: 128 ident: bib2 article-title: International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee report on inborn errors of immunity publication-title: J Clin Immunol – volume: 9 start-page: 588 year: 2018 ident: bib24 article-title: CEBPE-mutant specific granule deficiency correlates with aberrant granule organization and substantial proteome alterations in neutrophils publication-title: Front Immunol – volume: 24 start-page: 50 year: 2018 end-page: 61 ident: bib10 article-title: cGAS drives noncanonical-inflammasome activation in age-related macular degeneration publication-title: Nat Med – volume: 490 start-page: 288 year: 2012 end-page: 291 ident: bib37 article-title: Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1 publication-title: Nature – volume: 140 start-page: 782 year: 2017 end-page: 796 ident: bib31 article-title: Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes publication-title: J Allergy Clin Immunol – volume: 49 start-page: 742 year: 2017 end-page: 752 ident: bib23 article-title: Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes publication-title: Nat Genet – volume: 101 start-page: e392 year: 2016 end-page: e396 ident: bib32 article-title: Specific antibody deficiency and autoinflammatory disease extend the clinical and immunological spectrum of heterozygous NFKB1 loss-of-function mutations in humans publication-title: Haematologica – year: 2011 ident: bib20 article-title: Digital multiplexed gene expression analysis using the NanoString nCounter system publication-title: Curr Protoc Mol Biol – volume: 127 start-page: 3154 year: 2016 end-page: 3164 ident: bib34 article-title: Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype publication-title: Blood – volume: 8 start-page: 36 year: 2017 ident: bib36 article-title: Canonical and non-canonical activation of NLRP3 inflammasome at the crossroad between immune tolerance and intestinal inflammation publication-title: Front Immunol – volume: 4 start-page: e1000014 year: 2008 ident: bib1 article-title: Translational systems biology of inflammation publication-title: PLoS Comput Biol – volume: 19 start-page: 125 year: 2001 end-page: 133 ident: bib21 article-title: The role of C/EBP(epsilon) in the terminal stages of granulocyte differentiation publication-title: Stem Cells – volume: 60 start-page: 3651 year: 2009 end-page: 3662 ident: bib27 article-title: Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta publication-title: Arthritis Rheum – volume: 94 start-page: 6462 year: 1997 end-page: 6467 ident: bib22 article-title: CCAAT/enhancer binding protein epsilon is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of promoters and differential splicing publication-title: Proc Natl Acad Sci U S A – volume: 16 start-page: 7 year: 2016 end-page: 21 ident: bib5 article-title: Converging roles of caspases in inflammasome activation, cell death and innate immunity publication-title: Nat Rev Immunol – year: 1969 ident: bib33 article-title: H. J. Conn's biological stains: a handbook on the nature and uses of the dyes employed in the biological laboratory – volume: 38 start-page: 129 year: 2018 end-page: 143 ident: bib3 article-title: The 2017 IUIS phenotypic classification for primary immunodeficiencies publication-title: J Clin Immunol – volume: 32 start-page: 90 year: 2015 end-page: 105 ident: bib4 article-title: Immunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind publication-title: Curr Opin Immunol – volume: 9 start-page: 1188 year: 2018 ident: bib19 article-title: An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations publication-title: Nat Commun – volume: 36 start-page: 326 year: 1979 end-page: 333 ident: bib18 article-title: Impaired neutrophil chemotaxis in Pelger-Huet anomaly publication-title: Clin Exp Immunol – volume: 287 start-page: 34474 year: 2012 end-page: 34483 ident: bib6 article-title: Toll or interleukin-1 receptor (TIR) domain-containing adaptor inducing interferon-beta (TRIF)-mediated caspase-11 protease production integrates Toll-like receptor 4 (TLR4) protein- and Nlrp3 inflammasome-mediated host defense against enteropathogens publication-title: J Biol Chem – volume: 43 start-page: 871 year: 1974 end-page: 874 ident: bib16 article-title: Recurrent attacks of abdominal pain and fever with familial segmentation arrest of granulocytes publication-title: Blood – volume: 221 start-page: 341 year: 2016 end-page: 346 ident: bib28 article-title: NLRP12 is a neutrophil-specific, negative regulator of in vitro cell migration but does not modulate LPS- or infection-induced NF-kappaB or ERK signalling publication-title: Immunobiology – volume: 97 start-page: 389 year: 2015 end-page: 403 ident: bib30 article-title: Haploinsufficiency of the NF-kappaB1 Subunit p50 in Common Variable Immunodeficiency publication-title: Am J Hum Genet – volume: 93 start-page: 3096 year: 1999 end-page: 3105 ident: bib13 article-title: CCAAT/enhancer binding protein epsilon is critical for effective neutrophil-mediated response to inflammatory challenge publication-title: Blood – volume: 15 start-page: 429 year: 2015 end-page: 440 ident: bib38 article-title: Aicardi-Goutieres syndrome and the type I interferonopathies publication-title: Nat Rev Immunol – volume: 525 start-page: 206 year: 2015 end-page: 211 ident: bib25 article-title: Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth publication-title: Nature – volume: 19 start-page: 180 year: 2018 ident: bib26 article-title: Proteinase 3; a potential target in chronic obstructive pulmonary disease and other chronic inflammatory diseases publication-title: Respir Res – volume: 150 start-page: 606 year: 2012 end-page: 619 ident: bib8 article-title: TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria publication-title: Cell – volume: 509 start-page: 366 year: 2014 end-page: 370 ident: bib7 article-title: Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases publication-title: Nature – volume: 35 start-page: 30 year: 1996 end-page: 38 ident: bib35 article-title: A novel human CCAAT/enhancer binding protein gene, C/EBPepsilon, is expressed in cells of lymphoid and myeloid lineages and is localized on chromosome 14q11.2 close to the T-cell receptor alpha/delta locus publication-title: Genomics – volume: 34 start-page: 213 year: 2011 end-page: 223 ident: bib39 article-title: Type I interferon inhibits interleukin-1 production and inflammasome activation publication-title: Immunity – volume: 39 start-page: 274 year: 1987 end-page: 277 ident: bib17 article-title: Impaired heme synthesis in a family with Pelger-Huet anomaly, recurrent abdominal pain attacks and impaired neutrophil motility in vitro publication-title: Eur J Haematol – volume: 97 start-page: 2561 year: 2001 end-page: 2567 ident: bib12 article-title: Neutrophil-specific granule deficiency: homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein-epsilon publication-title: Blood – volume: 94 start-page: 13187 year: 1997 end-page: 13192 ident: bib15 article-title: Impaired granulopoiesis, myelodysplasia, and early lethality in CCAAT/enhancer binding protein epsilon-deficient mice publication-title: Proc Natl Acad Sci U S A – volume: 4 start-page: 1503 year: 2005 end-page: 1521 ident: bib29 article-title: Proteomic analysis of human neutrophil granules publication-title: Mol Cell Proteomics – volume: 113 start-page: 317 year: 2009 end-page: 327 ident: bib11 article-title: Human C/EBP-epsilon activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation publication-title: Blood |
| SSID | ssj0009389 |
| Score | 2.4921556 |
| Snippet | CCAAT enhancer–binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only... CCAAT enhancer-binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only... BackgroundCCAAT enhancer–binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The... |
| SourceID | swepub pubmedcentral proquest pubmed elsevier |
| SourceType | Open Access Repository Aggregation Database Index Database Publisher |
| StartPage | 1364 |
| SubjectTerms | Abdomen Age Aged autoinflammatory diseases Bacterial infections Caspase-5 Caspases - genetics Caspases - metabolism CCAAT-Enhancer-Binding Proteins - genetics Cells, Cultured chemotaxis Chromatin Deoxyribonucleic acid DNA Female Fever Flow cytometry Gain of Function Mutation - genetics gain-of-function mutation Gene Expression Profiling Genetic analysis Genomes Granulocytes hereditary Hospitals Human subjects Humans Immune system Immunodeficiency Immunologic deficiency syndromes Immunologic Deficiency Syndromes - genetics Immunoprecipitation Infections Inflammasomes Inflammasomes - genetics Inflammasomes - metabolism Inflammation Inflammation - genetics interferons Lymphatic system Macrophages Macrophages - metabolism Macrophages - pathology Male Microscopy Mutation neomorphic mutation Neutrophils Neutrophils - physiology NLR family NLR Family, Pyrin Domain-Containing 3 Protein - genetics NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Pain Pedigree Proteins Proteomics pyrin domain-containing 3 protein Pyrin protein Repressors Ribonucleic acid RNA Sequence Analysis, RNA Transcription factors Ulcers Up-Regulation |
| Title | Gain-of-function CEBPE mutation causes noncanonical autoinflammatory inflammasomopathy |
| URI | https://www.clinicalkey.com/#!/content/1-s2.0-S0091674919307626 https://dx.doi.org/10.1016/j.jaci.2019.06.003 https://www.ncbi.nlm.nih.gov/pubmed/31201888 https://www.proquest.com/docview/2312227773 https://www.proquest.com/docview/2272218225 https://pubmed.ncbi.nlm.nih.gov/PMC11057357 http://kipublications.ki.se/Default.aspx?queryparsed=id:142226366 |
| Volume | 144 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELaqIiEuiDcLpQoS4haa-FHbx7LasoBacaCoN8txbLGtNqnYzYELv50Z29kq6gGJWxx7pGRmPPONPDMm5B0LrGZC6rKxrCq5qFypGgsxj6OiaRrweQzrnc_Oj5cX_MuluNwj87EWBtMqs-1PNj1a6_zmKHPz6Ga1whpfjSn0GiAIBOMU225zLlHLP_y5TfPQTCUIrOsSV-fCmZTjdWXdCtO7dOzhGS_OuvVIdxHn3cTJSXvR6JJOH5GHGUsWJ-lzH5M93z0h98_yaflT8uMThP1lH0p0XiiAYr74-G1RrId0_l44O2z8puj6DhjcxwrJwg7bHrQOFGUdD-CLcbDp1z3eX_z7Gbk4XXyfL8t8j0LpBZfbMnCIMdogAhbFWh-oD03gVZAQu0ntvOWili3VwlWtBBkBZASQoLVvVNuKVrHnZB8-wr8khW5pAK93bJ3z3DHY7crZllMZVMMtZzPCRgaasbQTjJEB-2zGfLIrg2w3yHYTk-qASuyoJsL_J93BKCOTt97GAGDF-l4pYfrtbho2DZ6E2M73A6yhkmLreipm5EUSqblJ3T0MkFe1UmpG1ETYuwXYkHs6061-xsbcNV6aDJo_I--TXkxo8qtrePKGSw1I6tV__vhr8gBHqSbygOxvfw3-DYCjbXMYtf-Q3Dv5_HV5_he36xFE |
| linkProvider | Elsevier |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3fb9MwED6NTgJeEL8pDAgS4s1aEtu1_Tiqjo6tFQ8b2pvlOLbWoSbT2jzsv-ecOJ2iPSDxlsQ5Kbmz776T7zsDfKWeZpQLRQpDU8J4aoksDOY8NudFUWDMo4HvvFhO5hfs5yW_3INpz4UJZZXR93c-vfXW8clh1ObhzWoVOL4qlNArhCCYjOeTR7AfulPxEewfnZzOl_e9d6nsULDKSBCI3JmuzOva2FWo8FJtG8_27Kz7oPQQdD6snRx0GG2j0vFzeBbhZHLUffEL2HPVS3i8iBvmr-D3D8z8Se1JiF_BBsl09v3XLFk33RZ8Yk2zcZukqivUcd2SJBPTbGuceDhX1u0efNLfbOp1HY4wvnsNF8ez8-mcxKMUiEOVbIlnmGaUnvvAizXO584XnqVeYPomlHWG8UyUueI2LQWaCVEj4gSlXCHLkpeSvoERfoR7B4kqc4-Bb2KsdcxSXPDSmpLlwsuCGUbHQHsF6p7dif5Io4vWfUnZtQ5q10Htuq2rQym-kxrY_59yB72NdFx9G42YNVB8hcDhL7thXDdhM8RUrm7wnVzkoXt9zsfwtjOpvukafGgUTzMp5RjkwNi7F0JP7uFItbpqe3Nn4dxknPxj-NbNi4FMfPQHr5xmQiGYev-fP_4ZnszPF2f67GR5-gGehpGOInkAo-1t4z4iVtoWn-Ja-AsArxP1 |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Gain-of-function+CEBPE+mutation+causes+noncanonical+autoinflammatory+inflammasomopathy&rft.jtitle=Journal+of+allergy+and+clinical+immunology&rft.au=G%C3%B6%C3%B6s%2C+Helka&rft.au=Fogarty%2C+Christopher+L.&rft.au=Sahu%2C+Biswajyoti&rft.au=Plagnol%2C+Vincent&rft.date=2019-11-01&rft.pub=Elsevier+Inc&rft.issn=0091-6749&rft.volume=144&rft.issue=5&rft.spage=1364&rft.epage=1376&rft_id=info:doi/10.1016%2Fj.jaci.2019.06.003&rft.externalDocID=S0091674919307626 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0091-6749&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0091-6749&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0091-6749&client=summon |