{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:45Z","timestamp":1785437025402,"version":"3.56.0"},"reference-count":28,"publisher":"Rockefeller University Press","issue":"5","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"German Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["01GM2206D"],"award-info":[{"award-number":["01GM2206D"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014840","name":"Joint Federal Committee","doi-asserted-by":"publisher","award":["01NVF21117"],"award-info":[{"award-number":["01NVF21117"]}],"id":[{"id":"10.13039\/501100014840","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,7]]},"abstract":"<jats:p>Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease with diverse phenotypes. We describe the genetics, phenotypes, and treatment of n = 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.<\/jats:p>","DOI":"10.70962\/jhi.20250108","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:21:56Z","timestamp":1779344516000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["ADA2 genotype and enzyme activity may predict vasculitic or hematologic DADA2 phenotype"],"prefix":"10.70962","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7395-8602","authenticated-orcid":true,"given":"Philipp","family":"Peters","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05591te55","id-type":"ROR","asserted-by":"publisher"}],"name":"Dr. von Hauner Children\u2019s Hospital, University Hospital, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen 1 Department of Pediatrics, , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0016-4760","authenticated-orcid":true,"given":"Johanna","family":"Schepp","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05emabm63","id-type":"ROR","asserted-by":"publisher"}],"name":"University Medical Center, University Ulm 2 Department of Pediatrics and Adolescent Medicine, , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9143-3263","authenticated-orcid":true,"given":"Michael H.","family":"Albert","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05591te55","id-type":"ROR","asserted-by":"publisher"}],"name":"Dr. von Hauner Children\u2019s Hospital, University Hospital, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen 1 Department of Pediatrics, , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5812-7675","authenticated-orcid":true,"given":"Horst","family":"von Bernuth","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Charit\u00e9 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,","place":["Germany"]},{"name":"Labor Berlin Charit\u00e9-Vivantes, 4 Department of Immunology, Berlin,","place":["Germany"]},{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies 5 , Berlin,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health 6 , Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-1690","authenticated-orcid":true,"given":"Norbert","family":"Blank","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013czdx64","id-type":"ROR","asserted-by":"publisher"}],"name":"Internal Medicine V, University Hospital Heidelberg 7 Department of Hematology, Oncology and Rheumatology, , Heidelberg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0362-7514","authenticated-orcid":true,"given":"J\u00fcrgen","family":"Brunner","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05wjv2104","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical University Innsbruck 8 Department of Pediatrics, , Innsbruck,","place":["Austria"]},{"name":"Danube Private University 9 Faculty of Medicine and Dentistry, , Krems,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-6010","authenticated-orcid":true,"given":"Gregor","family":"D\u00fcckers","sequence":"additional","affiliation":[{"name":"Kinderarztpraxis Am Venner Markt 10 , M\u00f6nchengladbach,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8737-001X","authenticated-orcid":true,"given":"Lisa","family":"Ehlers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Charit\u00e9 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,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health 6 , Berlin,","place":["Germany"]},{"name":"German Rheumatology Research Center Berlin - A Leibniz Institute, 11 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8441-1784","authenticated-orcid":true,"given":"Susan","family":"Farmand","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01zgy1s35","id-type":"ROR","asserted-by":"publisher"}],"name":"University Medical Center Hamburg 12 Division of Pediatric Stem Cell Transplantation and Immunology, Department of Pediatric Hematology and Oncology, , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1946-3916","authenticated-orcid":true,"given":"Dirk","family":"F\u00f6ll","sequence":"additional","affiliation":[{"name":"University of Muenster 13 Department of Pediatric Rheumatology and Immunology, , M\u00fcnster,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8484-9890","authenticated-orcid":true,"given":"Elisabeth","family":"F\u00f6rster-Waldl","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Congenital Immunodeficiencies, Medical University of Vienna 14 Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Intensive Care and Neuropediatrics, , Vienna,","place":["Austria"]},{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Comprehensive Center for Inflammation and Immunity, Medical University of Vienna 15 , Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1827-1434","authenticated-orcid":true,"given":"Janina","family":"Gburek-Augustat","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028hv5492","id-type":"ROR","asserted-by":"publisher"}],"name":"Hospital for Children and Adolescents, University Hospital Leipzig 16 Division of Neuropaediatrics, , Leipzig,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5647-4262","authenticated-orcid":true,"given":"Sujal","family":"Ghosh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024z2rq82","id-type":"ROR","asserted-by":"publisher"}],"name":"Center of Child and Adolescent Health, Heinrich Heine University 17 Department for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0948-9047","authenticated-orcid":true,"given":"Lisa","family":"G\u00f6schl","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Comprehensive Center for Inflammation and Immunity, Medical University of Vienna 15 , Vienna,","place":["Austria"]},{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical University of Vienna 18 Division of Rheumatology, Department of Internal Medicine III, , Vienna,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6928-7973","authenticated-orcid":true,"given":"Marc","family":"H\u00f6mberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05mxhda18","id-type":"ROR","asserted-by":"publisher"}],"name":"University Children\u2019s Hospital of Cologne, Medical Faculty, University of Cologne 19 Department of Pediatric Oncology and Hematology, , Cologne,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9165-1690","authenticated-orcid":true,"given":"Manfred","family":"H\u00f6nig","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05emabm63","id-type":"ROR","asserted-by":"publisher"}],"name":"University Medical Center, University Ulm 2 Department of Pediatrics and Adolescent Medicine, , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2404-9397","authenticated-orcid":true,"given":"Tilmann","family":"Kallinich","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Charit\u00e9 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,","place":["Germany"]},{"name":"German Center for Child and Adolescent Health 6 , Berlin,","place":["Germany"]},{"name":"German Rheumatology Research Center Berlin - A Leibniz Institute, 11 Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5639-8690","authenticated-orcid":true,"given":"Christian","family":"Klemann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028hv5492","id-type":"ROR","asserted-by":"publisher"}],"name":"Hospital for Childrens and Adolescents, University of Leipzig 20 Department of Pediatric Immunology, Rheumatology and Infectiology, , Leipzig,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7285-7842","authenticated-orcid":true,"given":"Leah","family":"Klingel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/025vngs54","id-type":"ROR","asserted-by":"publisher"}],"name":"University Medicine Greifswald 21 Department of Pediatrics and Adolescent Medicine, , Greifswald,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-6772","authenticated-orcid":true,"given":"Udo","family":"Kontny","sequence":"additional","affiliation":[{"name":"Oncology and Stem Cell Transplantation, University Medical Center 22 Division of Pediatric Hematology, , Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2880-6320","authenticated-orcid":true,"given":"Lisa-Maria","family":"Kuhn","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024z2rq82","id-type":"ROR","asserted-by":"publisher"}],"name":"Center of Child and Adolescent Health, Heinrich Heine University 17 Department for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5929-868X","authenticated-orcid":true,"given":"Peter","family":"Lamprecht","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck 23 Department of Rheumatology and Clinical Immunology, , L\u00fcbeck,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2365-4341","authenticated-orcid":true,"given":"Kai","family":"Lehmberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01zgy1s35","id-type":"ROR","asserted-by":"publisher"}],"name":"University Medical Center Hamburg 12 Division of Pediatric Stem Cell Transplantation and Immunology, Department of Pediatric Hematology and Oncology, , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-8282","authenticated-orcid":true,"given":"Almut","family":"Meyer-Bahlburg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/025vngs54","id-type":"ROR","asserted-by":"publisher"}],"name":"University Medicine Greifswald 21 Department of Pediatrics and Adolescent Medicine, , Greifswald,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7477-6632","authenticated-orcid":true,"given":"Ingo","family":"M\u00fcller","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01zgy1s35","id-type":"ROR","asserted-by":"publisher"}],"name":"University Medical Center Hamburg 12 Division of Pediatric Stem Cell Transplantation and Immunology, Department of Pediatric Hematology and Oncology, , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1584-1115","authenticated-orcid":true,"given":"Michaela","family":"Nathrath","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048ycfv73","id-type":"ROR","asserted-by":"publisher"}],"name":"Psychosomatics and Systemic Diseases, Klinikum Kassel 24 Department of Pediatric Hemato-Oncology, , Kassel,","place":["Germany"]},{"id":[{"id":"https:\/\/ror.org\/05591te55","id-type":"ROR","asserted-by":"publisher"}],"name":"Klinikum Rechts der Isar, Technische Universit\u00e4t M\u00fcnchen 25 Children\u2019s Cancer Research Centre and Department of Pediatrics, , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9945-8833","authenticated-orcid":true,"given":"Tim","family":"Niehues","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01be19w37","id-type":"ROR","asserted-by":"publisher"}],"name":"Helios Klinikum Krefeld, Affiliated with Rheinisch-Westf\u00e4lische Technische Hochschule University Aachen 26 Centre for Child and Adolescent Health, , Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2893-7252","authenticated-orcid":true,"given":"Prasad T.","family":"Oommen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024z2rq82","id-type":"ROR","asserted-by":"publisher"}],"name":"Center of Child and Adolescent Health, Heinrich Heine University 17 Department for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6653-9047","authenticated-orcid":true,"given":"Jana","family":"Pachlopnik Schmid","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035vb3h42","id-type":"ROR","asserted-by":"publisher"}],"name":"University Children\u2019s Hospital Zurich, and Pediatric Immunology, Faculty of Medicine, University of Zurich 27 Division of Immunology and Children\u2019s Research Center, , Zurich,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2950-5411","authenticated-orcid":true,"given":"Seraina","family":"Prader","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035vb3h42","id-type":"ROR","asserted-by":"publisher"}],"name":"University Children\u2019s Hospital Zurich, and Pediatric Immunology, Faculty of Medicine, University of Zurich 27 Division of Immunology and Children\u2019s Research Center, , Zurich,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1432-5183","authenticated-orcid":true,"given":"Alexander","family":"Puzik","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03vzbgh69","id-type":"ROR","asserted-by":"publisher"}],"name":"Children\u2019s Hospital, Medical Center \u2013 University of Freiburg, Faculty of Medicine, University of Freiburg 28 Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5041-2308","authenticated-orcid":true,"given":"Raffaele","family":"Renella","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05a353079","id-type":"ROR","asserted-by":"publisher"}],"name":"University Hospital of Lausanne 29 Division of Pediatrics, Pediatric Hematology-Oncology Unit, , Lausanne,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7798-7996","authenticated-orcid":true,"given":"Ansgar","family":"Schulz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05emabm63","id-type":"ROR","asserted-by":"publisher"}],"name":"University Medical Center, University Ulm 2 Department of Pediatrics and Adolescent Medicine, , Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7797-3124","authenticated-orcid":true,"given":"Andrea","family":"Skrabl-Baumgartner","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00pw0pp06","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical University Graz 30 Department of Pediatrics and Adolescent Medicine, , Graz,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1719-7554","authenticated-orcid":true,"given":"Sven","family":"Starke","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/028hv5492","id-type":"ROR","asserted-by":"publisher"}],"name":"University Hospital Leipzig, University of Leipzig 31 Department of Pediatric Oncology, Hematology and Hemostaseology, , Leipzig,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4067-5363","authenticated-orcid":true,"given":"Teresa K.","family":"Tarrant","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke University School of Medicine 32 Division of Rheumatology and Immunology, Department of Medicine, , Durham, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-8554","authenticated-orcid":true,"given":"Michael","family":"Hershfield","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00py81415","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke University School of Medicine 32 Division of Rheumatology and Immunology, Department of Medicine, , Durham, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6897-6806","authenticated-orcid":true,"given":"Bodo","family":"Grimbacher","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03vzbgh69","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg 33 Institute for Immunodeficiency, Center for Chronic Immunodeficiency, , Freiburg,","place":["Germany"]},{"id":[{"id":"https:\/\/ror.org\/03vzbgh69","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Chronic ImmunodefiVical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg 34 Clinic of Rheumatology and Clinical Immunology, , Freiburg,","place":["Germany"]},{"name":"German Center for Infection Research, Satellite Center Freiburg 35 , Freiburg,","place":["Germany"]},{"name":"Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University 36 , Freiburg,","place":["Germany"]},{"name":"RESIST \u2013 Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg 37 , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9644-2003","authenticated-orcid":true,"given":"Fabian","family":"Hauck","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05591te55","id-type":"ROR","asserted-by":"publisher"}],"name":"Dr. von Hauner Children\u2019s Hospital, University Hospital, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen 1 Department of Pediatrics, , Munich,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"2026061609031130900_bib1","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1007\/s10875-022-01289-3","article-title":"Human inborn errors of immunity: 2022 update on the classification from the international union of immunological societies expert committee","volume":"42","author":"Tangye","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"2026061609031130900_bib2","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.jaci.2021.04.034","article-title":"Comprehensive analysis of ADA2 genetic variants and estimation of carrier frequency driven by a function-based approach","volume":"149","author":"Jee","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026061609031130900_bib3","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1056\/NEJMoa1307361","article-title":"Early-onset stroke and vasculopathy associated with mutations in ADA2","volume":"370","author":"Zhou","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"2026061609031130900_bib4","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1056\/nejmoa1307362","article-title":"Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy","volume":"370","author":"Navon Elkan","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"2026061609031130900_bib5","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/j.1365-2249.2004.02591.x","article-title":"Macrophages are a source of extracellular adenosine deaminase-2 during inflammatory responses","volume":"138","author":"Conlon","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"2026061609031130900_bib6","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1042\/BJ20050683","article-title":"Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity","volume":"391","author":"Zavialov","year":"2005","journal-title":"Biochem. J."},{"key":"2026061609031130900_bib7","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1515\/BC.2006.042","article-title":"Human plasma adenosine deaminase 2 is secreted by activated monocytes","volume":"387","author":"Iwaki-Egawa","year":"2006","journal-title":"Biol. Chem."},{"key":"2026061609031130900_bib8","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1073\/pnas.75.1.446","article-title":"Characterization of the residual adenosine deaminating activity in the spleen of a patient with combined immunodeficiency disease and adenosine deaminase deficiency","volume":"75","author":"Schrader","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026061609031130900_bib9","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1182\/blood.V72.5.1627.1627","article-title":"Differential expression of adenosine deaminase isozymes in acute leukemia","volume":"72","author":"Ratech","year":"1988","journal-title":"Blood"},{"key":"2026061609031130900_bib10","doi-asserted-by":"publisher","first-page":"3883","DOI":"10.1007\/s10067-021-05711-w","article-title":"Expanding spectrum of DADA2: A review of phenotypes, genetics, pathogenesis and treatment","volume":"40","author":"Pinto","year":"2021","journal-title":"Clin. Rheumatol."},{"key":"2026061609031130900_bib11","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.jaci.2023.04.014","article-title":"Comparison of disease phenotypes and mechanistic insight on causal variants in patients with DADA2","volume":"152","author":"Chen","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026061609031130900_bib12","doi-asserted-by":"publisher","first-page":"114899","DOI":"10.1016\/j.celrep.2024.114899","article-title":"ADA2 is a lysosomal deoxyadenosine deaminase acting on DNA involved in regulating TLR9-mediated immune sensing of DNA","volume":"43","author":"Greiner-Tollersrud","year":"2024","journal-title":"Cell Rep."},{"key":"2026061609031130900_bib13","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1016\/j.jaci.2019.12.908","article-title":"Genotype and functional correlates of disease phenotype in deficiency of adenosine deaminase 2 (DADA2)","volume":"145","author":"Lee","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026061609031130900_bib14","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1007\/s10875-021-01098-0","article-title":"Hematopoietic cell transplantation cures adenosine deaminase 2 deficiency: Report on 30 patients","volume":"41","author":"Hashem","year":"2021","journal-title":"J. Clin. Immunol."},{"key":"2026061609031130900_bib15","doi-asserted-by":"publisher","first-page":"3174","DOI":"10.1182\/bloodadvances.2020003811","article-title":"Lentiviral correction of enzymatic activity restrains macrophage inflammation in adenosine deaminase 2 deficiency","volume":"5","author":"Zoccolillo","year":"2021","journal-title":"Blood Adv."},{"key":"2026061609031130900_bib16","doi-asserted-by":"publisher","first-page":"852830","DOI":"10.3389\/fimmu.2022.852830","article-title":"Lentiviral mediated ADA2 gene transfer corrects the defects associated with deficiency of adenosine deaminase type 2","volume":"13","author":"Hong","year":"2022","journal-title":"Front. Immunol."},{"key":"2026061609031130900_bib17","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/s0022-3476(97)70200-2","article-title":"Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations","volume":"130","author":"Comans-Bitter","year":"1997","journal-title":"J. Pediatr."},{"key":"2026061609031130900_bib18","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.15894","article-title":"Evaluation and management of deficiency of adenosine deaminase 2: An international consensus statement","volume":"6","author":"Lee","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"2026061609031130900_bib19","doi-asserted-by":"publisher","first-page":"811473","DOI":"10.3389\/fimmu.2021.811473","article-title":"The spectrum of the deficiency of adenosine deaminase 2: An observational analysis of a 60 patient cohort","volume":"12","author":"Barron","year":"2022","journal-title":"Front. Immunol."},{"key":"2026061609031130900_bib20","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/s10875-018-0525-8","article-title":"Deficiency of adenosine deaminase 2 (DADA2): Updates on the phenotype, genetics, pathogenesis, and treatment","volume":"38","author":"Meyts","year":"2018","journal-title":"J. Clin. Immunol."},{"key":"2026061609031130900_bib21","doi-asserted-by":"publisher","first-page":"13","DOI":"10.18176\/jiaci.0748","article-title":"Treatment and outcome in deficiency of adenosine deaminase 2: A literature review","volume":"32","author":"Zhang","year":"2022","journal-title":"J. Investig. Allergy Clin. Immunol."},{"key":"2026061609031130900_bib22","doi-asserted-by":"publisher","first-page":"2682","DOI":"10.1182\/blood-2017-07-798660","article-title":"Hematopoietic stem cell transplantation rescues the hematological, immunological, and vascular phenotype in DADA2","volume":"130","author":"Hashem","year":"2017","journal-title":"Blood"},{"key":"2026061609031130900_bib28","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1093\/rheumatology\/keac233","article-title":"Early onset is an indication of the severity of DADA2 disease","volume":"62","author":"Zhao","year":"2023","journal-title":"Rheumatology"},{"key":"2026061609031130900_bib23","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1007\/s10875-023-01521-8","article-title":"Clinical symptoms, laboratory parameters and long-term follow-up in a national DADA2 cohort","volume":"43","author":"Andriessen","year":"2023","journal-title":"J. Clin. Immunol."},{"key":"2026061609031130900_bib24","article-title":"DADA2 Patient Registry","author":"DADA2 Foundation","year":"2023"},{"key":"2026061609031130900_bib25","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.jpeds.2016.06.058","article-title":"Extending the clinical phenotype of adenosine deaminase 2 deficiency","volume":"177","author":"Ben-Ami","year":"2016","journal-title":"J. Pediatr."},{"key":"2026061609031130900_bib26","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1002\/art.40147","article-title":"Screening of 181 patients with antibody deficiency for deficiency of adenosine deaminase 2 sheds new light on the disease in adulthood","volume":"69","author":"Schepp","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"2026061609031130900_bib27","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1002\/art.41549","article-title":"Sequence-based screening of patients with idiopathic polyarteritis nodosa, granulomatosis with polyangiitis, and microscopic polyangiitis for deleterious genetic variants in ADA2","volume":"73","author":"Schnappauf","year":"2021","journal-title":"Arthritis Rheumatol."}],"container-title":["Journal of Human Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jhi\/article-pdf\/doi\/10.70962\/jhi.20250108\/2036653\/jhi_20250108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jhi\/article-pdf\/doi\/10.70962\/jhi.20250108\/2036653\/jhi_20250108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T13:03:20Z","timestamp":1781615000000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jhi\/article\/2\/5\/e20250108\/282740\/ADA2-genotype-and-enzyme-activity-may-predict"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9,7]]}},"URL":"https:\/\/doi.org\/10.70962\/jhi.20250108","relation":{},"ISSN":["3065-8993"],"issn-type":[{"value":"3065-8993","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"article-number":"e20250108"}}