ADA2 genotype and enzyme activity may predict vasculitic or hematologic DADA2 phenotype

Journal of Human Immunity, vol. 2, pp. e20250108

Abstract

= 48 DADA2 patients from Germany, Austria, and Switzerland. We report a high incidence of hematological (83%) and immunological features (85%), a comparatively low anti-tumor necrosis factor full-response rate (58%), and a high decision probability (21%) for hematopoietic cell transplantation (HCT). We establish a correlation between genetic variant ADA2 activity and patient ADA2 activity. Remarkably, lower patient ADA2 activity is predictive of neutropenia and shows a trend toward HCT decision, whereas higher patient ADA2 activity is predictive of vasculitis symptoms. Genetic variants with low residual ADA2 activity are significantly more common among patients receiving HCT. Our study corroborates previous observations connecting ADA2 activity and clinical phenotype, which up to now have been mainly based on in vitro data.

Authors 39

1. Philipp Peters

   LMU Klinikum · Ludwig-Maximilians-Universität München

   Affiliation as printed

   Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München 1 Department of Pediatrics, , Munich,

2. Johanna Schepp

   Universität Ulm

   Affiliation as printed

   University Medical Center, University Ulm 2 Department of Pediatrics and Adolescent Medicine, , Ulm,

3. Michael H. Albert

   LMU Klinikum · Ludwig-Maximilians-Universität München

   Affiliation as printed

   Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München 1 Department of Pediatrics, , Munich,

4. Horst von Bernuth

   Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies 5 , Berlin,

   Charité University Medicine, Berlin, Corporate Member of Free University and Humboldt University and Berlin Institute of Health 3 Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, , Berlin,

   German Center for Child and Adolescent Health 6 , Berlin,

   Labor Berlin Charité-Vivantes, 4 Department of Immunology, Berlin,

5. Norbert Blank

   Heidelberg University · University Hospital Heidelberg

   Affiliation as printed

   Internal Medicine V, University Hospital Heidelberg 7 Department of Hematology, Oncology and Rheumatology, , Heidelberg,

6. Jürgen Brunner

   Danube Private University · Innsbruck Medical University

   Affiliation as printed

   Danube Private University 9 Faculty of Medicine and Dentistry, , Krems,

   Medical University Innsbruck 8 Department of Pediatrics, , Innsbruck,

7. Gregor Dückers
   Affiliation as printed

   Kinderarztpraxis Am Venner Markt 10 , Mönchengladbach,

8. Lisa Ehlers

   German Rheumatism Research Centre · Charité - Universitätsmedizin Berlin

   Affiliation as printed

   Charité University Medicine, Berlin, Corporate Member of Free University and Humboldt University and Berlin Institute of Health 3 Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, , Berlin,

   German Center for Child and Adolescent Health 6 , Berlin,

   German Rheumatology Research Center Berlin - A Leibniz Institute, 11 Berlin,

9. Susan Farmand

   Universität Hamburg

   Affiliation as printed

   University Medical Center Hamburg 12 Division of Pediatric Stem Cell Transplantation and Immunology, Department of Pediatric Hematology and Oncology, , Hamburg,

10. Dirk Foell

    University of Münster

    Affiliation as printed

    University of Muenster 13 Department of Pediatric Rheumatology and Immunology, , Münster,

11. Elisabeth Förster‐Waldl

    Medical University of Vienna

    Affiliation as printed

    Center for Congenital Immunodeficiencies, Medical University of Vienna 14 Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Intensive Care and Neuropediatrics, , Vienna,

    Comprehensive Center for Inflammation and Immunity, Medical University of Vienna 15 , Vienna,

12. Janina Gburek‐Augustat

    University Hospital Leipzig

    Affiliation as printed

    Hospital for Children and Adolescents, University Hospital Leipzig 16 Division of Neuropaediatrics, , Leipzig,

13. Sujal Ghosh

    Heinrich Heine University Düsseldorf

    Affiliation as printed

    Center of Child and Adolescent Health, Heinrich Heine University 17 Department for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, , Düsseldorf,

14. Lisa Göschl

    Medical University of Vienna

    Affiliation as printed

    Comprehensive Center for Inflammation and Immunity, Medical University of Vienna 15 , Vienna,

    Medical University of Vienna 18 Division of Rheumatology, Department of Internal Medicine III, , Vienna,

15. Marc Hoemberg

    University of Cologne

    Affiliation as printed

    University Children’s Hospital of Cologne, Medical Faculty, University of Cologne 19 Department of Pediatric Oncology and Hematology, , Cologne,

16. Manfred Hoenig

    Universität Ulm

    Affiliation as printed

    University Medical Center, University Ulm 2 Department of Pediatrics and Adolescent Medicine, , Ulm,

17. Tilmann Kallinich

    German Rheumatism Research Centre · Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Charité University Medicine, Berlin, Corporate Member of Free University and Humboldt University and Berlin Institute of Health 3 Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, , Berlin,

    German Center for Child and Adolescent Health 6 , Berlin,

    German Rheumatology Research Center Berlin - A Leibniz Institute, 11 Berlin,

18. Christian Klemann

    University Hospital Leipzig · Leipzig University

    Affiliation as printed

    Hospital for Childrens and Adolescents, University of Leipzig 20 Department of Pediatric Immunology, Rheumatology and Infectiology, , Leipzig,

19. Leah Bernadette Klingel

    Universitätsmedizin Greifswald · Universität Greifswald

    Affiliation as printed

    University Medicine Greifswald 21 Department of Pediatrics and Adolescent Medicine, , Greifswald,

20. Udo Kontny Aachen Oncology and Stem Cell Transplantation

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Oncology and Stem Cell Transplantation, University Medical Center 22 Division of Pediatric Hematology, , Aachen,

21. Lisa Maria Kuhn

    Heinrich Heine University Düsseldorf

    Affiliation as printed

    Center of Child and Adolescent Health, Heinrich Heine University 17 Department for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, , Düsseldorf,

22. Peter Lamprecht

    University of Lübeck

    Affiliation as printed

    University of Lübeck 23 Department of Rheumatology and Clinical Immunology, , Lübeck,

23. Kai Lehmberg

    Universität Hamburg

    Affiliation as printed

    University Medical Center Hamburg 12 Division of Pediatric Stem Cell Transplantation and Immunology, Department of Pediatric Hematology and Oncology, , Hamburg,

24. Almut Meyer‐Bahlburg

    Universitätsmedizin Greifswald · Universität Greifswald

    Affiliation as printed

    University Medicine Greifswald 21 Department of Pediatrics and Adolescent Medicine, , Greifswald,

25. Ingo Müller

    Universität Hamburg

    Affiliation as printed

    University Medical Center Hamburg 12 Division of Pediatric Stem Cell Transplantation and Immunology, Department of Pediatric Hematology and Oncology, , Hamburg,

26. Michaela Nathrath

    TUM Klinikum · Klinikum Kassel · Technical University of Munich

    Affiliation as printed

    Klinikum Rechts der Isar, Technische Universität München 25 Children’s Cancer Research Centre and Department of Pediatrics, , Munich,

    Psychosomatics and Systemic Diseases, Klinikum Kassel 24 Department of Pediatric Hemato-Oncology, , Kassel,

27. Tim Niehues Aachen Helios Klinikum Krefeld

    Helios Klinikum Krefeld · RWTH Aachen University

    Affiliation as printed

    Helios Klinikum Krefeld, Affiliated with Rheinisch-Westfälische Technische Hochschule University Aachen 26 Centre for Child and Adolescent Health, , Aachen,

28. Prasad T. Oommen

    Heinrich Heine University Düsseldorf

    Affiliation as printed

    Center of Child and Adolescent Health, Heinrich Heine University 17 Department for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, , Düsseldorf,

29. Jana Pachlopnik Schmid

    University of Zurich · University Children's Hospital Zurich

    Affiliation as printed

    University Children’s Hospital Zurich, and Pediatric Immunology, Faculty of Medicine, University of Zurich 27 Division of Immunology and Children’s Research Center, , Zurich,

30. Seraina Prader

    University of Zurich · University Children's Hospital Zurich

    Affiliation as printed

    University Children’s Hospital Zurich, and Pediatric Immunology, Faculty of Medicine, University of Zurich 27 Division of Immunology and Children’s Research Center, , Zurich,

31. Alexander Puzik

    University of Freiburg · University Medical Center Freiburg

    Affiliation as printed

    Children’s Hospital, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg 28 Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, , Freiburg,

32. Raffaele Renella

    Centre Hospitalier Universitaire Vaudois

    Affiliation as printed

    University Hospital of Lausanne 29 Division of Pediatrics, Pediatric Hematology-Oncology Unit, , Lausanne,

33. Ansgar Schulz

    Universität Ulm

    Affiliation as printed

    University Medical Center, University Ulm 2 Department of Pediatrics and Adolescent Medicine, , Ulm,

34. Andrea Skrabl‐Baumgartner

    Medical University of Graz

    Affiliation as printed

    Medical University Graz 30 Department of Pediatrics and Adolescent Medicine, , Graz,

35. Sven Starke

    University Hospital Leipzig · Leipzig University

    Affiliation as printed

    University Hospital Leipzig, University of Leipzig 31 Department of Pediatric Oncology, Hematology and Hemostaseology, , Leipzig,

36. Teresa K. Tarrant

    Duke University

    Affiliation as printed

    Duke University School of Medicine 32 Division of Rheumatology and Immunology, Department of Medicine, , Durham, NC,

37. Michael Steven Hershfield

    Duke University

    Affiliation as printed

    Duke University School of Medicine 32 Division of Rheumatology and Immunology, Department of Medicine, , Durham, NC,

38. Bodo Grimbacher

    University of Freiburg · University Medical Center Freiburg · German Center for Infection Research

    Affiliation as printed

    Center for Chronic ImmunodefiVical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg 34 Clinic of Rheumatology and Clinical Immunology, , Freiburg,

    Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University 36 , Freiburg,

    German Center for Infection Research, Satellite Center Freiburg 35 , Freiburg,

    Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg 33 Institute for Immunodeficiency, Center for Chronic Immunodeficiency, , Freiburg,

    RESIST – Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg 37 , Freiburg,

39. Fabian H. Hauck

    LMU Klinikum · Ludwig-Maximilians-Universität München

    Affiliation as printed

    Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München 1 Department of Pediatrics, , Munich,