Evidence map›Paper›PMID 26025129›Full record

ArticleThe Journal of allergy and clinical immunology2015

Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases.

Dirk Holzinger, Selina Kathleen Fassl, Wilco de Jager, Peter Lohse, Ute F Röhrig, Marco Gattorno, Alessia Omenetti, Sabrina Chiesa, Francesca Schena, Judith Austermann and 33 more

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In one paragraph

Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 122 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  7. Review
  8. Article
  9. Article
  10. Review
  11. S100A9: The Unusual Suspect Connecting Viral Infection and Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2024
    Review
  12. Review
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  14. The 4Pediatric rheumatology online journal · 2024
    Article
  15. Review
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  17. Article
  18. Article
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  20. Nature and nurture: understanding phenotypic variation in inborn errors of immunity.Frontiers in cellular and infection microbiology · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors at 20 institutions in 10 countries.

Dirk HolzingerInstitute of Immunology, University of Muenster, Muenster, Germany; Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, University of Muenster, Muenster, Germany; Department of Paediatric Rheumatology and Immunology, University Children's Hospital Muenster, University of Muenster, Muenster, Germany.
Selina Kathleen FasslInstitute of Immunology, University of Muenster, Muenster, Germany.
Wilco de JagerLaboratory for Translational Immunology, Department of Paediatric Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Peter LohseDepartment of Clinical Chemistry Großhadern, University of Munich, Munich, Germany.
Ute F RöhrigSwiss Institute of Bioinformatics, Molecular Modeling Group, Lausanne, Switzerland.
Marco Gattorno2nd Division of Pediatrics "G. Gaslini" Scientific Institute, Genoa, Italy.
Alessia Omenetti2nd Division of Pediatrics "G. Gaslini" Scientific Institute, Genoa, Italy.
Sabrina Chiesa2nd Division of Pediatrics "G. Gaslini" Scientific Institute, Genoa, Italy.
Francesca Schena2nd Division of Pediatrics "G. Gaslini" Scientific Institute, Genoa, Italy.
Judith AustermannInstitute of Immunology, University of Muenster, Muenster, Germany; Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, University of Muenster, Muenster, Germany.
Thomas VoglInstitute of Immunology, University of Muenster, Muenster, Germany; Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, University of Muenster, Muenster, Germany.
Douglas B KuhnsLeidos Biomedical Research, Frederick, Md.
Steven M HollandNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
Carlos Rodríguez-GallegoDepartment of Immunology, Hospital Universitario Son Espases, Palma de Mallorca, Spain.
Ricardo López-AlmarazDepartment of Pediatrics, Hospital Universitario de Canarias, La Laguna, Spain.
Juan I ArosteguiDepartment of Immunology-CDB, Hospital Clinic-IDIBAPS, Barcelona, Spain.
Elena ColinoDepartment of Paediatrics, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain.
Rosa RoldanDepartment of Pediatric Rheumatology Hospital Universitario Reina Sofia, Cordoba, Spain.
Smaragdi Fessatou3rd Department of Pediatrics, Athens University Medical School, "ATTIKON" Hospital, Athens, Greece.
Bertrand IsidorService de Génétique Médicale, Centre Hospitalo-Universitaire, Nantes, France.
Sylvaine PoignantService de Pédiatrie, CH Cholet, Cholet, France.
Koichi ItoDepartment of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
Hans-Joerg EppleDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Jonathan A BernsteinDepartment of Pediatrics, Stanford University School of Medicine, Stanford, Calif.
Michael JengDepartment of Pediatrics, Stanford University School of Medicine, Stanford, Calif.
Jennifer FrankovichDepartment of Pediatrics, Stanford University School of Medicine, Stanford, Calif.
Geraldina LionettiDepartment of Pediatrics, University of California, San Francisco, Calif.
Joseph A ChurchDivision of Clinical Immunology and Allergy, Children's Hospital Los Angeles and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, Calif.
Peck Y OngDivision of Clinical Immunology and Allergy, Children's Hospital Los Angeles and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, Calif.
Mona LaPlantChildren's Hospital and Clinics of Minnesota, Saint Paul, Minn.
Mario AbinunDepartment of Paediatric Immunology and Children's BMT Unit, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom; Institute of Clinical Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Rod SkinnerDepartment of Paediatric and Adolescent Haematology and Oncology and Children's BMT Unit, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom; Northern Institute of Cancer Research, University of Newcastle, Newcastle upon Tyne, United Kingdom.
Venetia BigleyHuman Dendritic Cell Laboratory, Newcastle University Medical School, Newcastle upon Tyne, United Kingdom.
Ulrich J SachsInstitute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany.
Claas HinzeInterdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, University of Muenster, Muenster, Germany; Deutsches Zentrum für Kinder-und Jugendrheumatologie, Garmisch-Partenkirchen, Germany.
Esther HoppenreijsDepartment of Paediatrics/Paediatric Rheumatology, St Maartenskliniek and Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Jan EhrchenInterdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, University of Muenster, Muenster, Germany; Department of Dermatology, University Hospital Muenster, Muenster, Germany; Department for Translational Dermatoinfectiology, University Hospital Muenster, Muenster, Germany.
Dirk FoellInterdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, University of Muenster, Muenster, Germany; Department of Paediatric Rheumatology and Immunology, University Children's Hospital Muenster, University of Muenster, Muenster, Germany.
Jae Jin ChaeNational Human Genome Research Institute, National Institutes of Health, Bethesda, Md.
Amanda OmbrelloNational Human Genome Research Institute, National Institutes of Health, Bethesda, Md.
Ivona AksentijevichNational Human Genome Research Institute, National Institutes of Health, Bethesda, Md.
Cord SunderkoetterInterdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, University of Muenster, Muenster, Germany; Department of Dermatology, University Hospital Muenster, Muenster, Germany; Department for Translational Dermatoinfectiology, University Hospital Muenster, Muenster, Germany.
Johannes RothInstitute of Immunology, University of Muenster, Muenster, Germany; Interdisciplinary Centre for Clinical Research IZKF, University Hospital Muenster, University of Muenster, Muenster, Germany. Electronic address: rothj@uni-muenster.de.
University Hospital Münster · DEIstituto Giannina Gaslini · ITNational Institutes of Health · USStanford University · USAugenstern · DEUniversity of Southern California · USCentre Hospitalier de Lens · FRCentre Hospitalier Universitaire de Nantes · FRCharité - Universitätsmedizin Berlin · DEChildren’s Minnesota - St. Paul Hospital · USGerman Center for Pediatric and Adolescent Rheumatology · DEGreat North Children's Hospital · GBHospital Clínic de Barcelona · ESHospital Universitario de Canarias · ESHospital Universitario Insular de Gran Canaria · ESHospital Universitario Reina Sofía · ESHospital Universitario Son Espases · ESInstitute of Cancer Research · GBJustus-Liebig-Universität Gießen · DELeidos (United States) · US

Funding

Genes And Gene Products As ImmunoadjuvantsZIAAI000647 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HOLLAND, STEVEN · 2009 to 2025
$22.6M
Transgenic Animal Models Of Human Immune DefectsZIAAI000646 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HOLLAND, STEVEN · 2009 to 2025
$22.2M
CCR NIH HHS HHSN261200800001CIntramural NIH HHSNCI NIH HHS HHSN261200800001EWellcome Trust 101155
6 · The paper itself

Abstract

backgroundHyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin).

objectiveWe sought to characterize the genetic cause and clinical spectrum of Hz/Hc.

methodsProline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA.

resultsThirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 ± 1300 μg/mL) compared with those with PAPA syndrome (116 ± 74 μg/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1.

conclusionMutations resulting in charge reversal in the y-domain of PSTPIP1 (E→K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.

Indexed as

Adaptor Proteins, Signal TransducingAdolescentAlarminsCalgranulin AChildCytokinesCytoskeletal ProteinsFemaleGenotypeHumansLeukocyte L1 Antigen ComplexMaleMetal Metabolism, Inborn ErrorsMutation, MissensePhenotypePhosphorylationAdaptor Proteins, Signal TransducingAlarminsCalgranulin ACytokinesCytoskeletal ProteinsLeukocyte L1 Antigen ComplexMEFV protein, humanPSTPIP1 protein, humanPyrinautoinflammationcalprotectingenotypeHyperzincemia and hypercalprotectinemiamyeloid-related protein 8/14phenotypeproline-serine-threonine phosphatase-interacting protein 1pyogenic arthritis, pyoderma gangrenosum, and acne syndromeS100 proteinszinc

Identifiers

PMID26025129
PMCPMC6591125
OpenAlexW2167386831

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.