The GAIN Registry - a New Prospective Study for Patients with Multi-organ Autoimmunity and Autoinflammation.

Autoimmunity Autoinflammation Epidemiology Immune-dysregulation Inborn error of immunity Primary immunodeficiency Rare diseases

Journal

Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137

Informations de publication

Date de publication:
08 2023
Historique:
received: 22 02 2023
accepted: 06 03 2023
medline: 21 7 2023
pubmed: 21 4 2023
entrez: 21 04 2023
Statut: ppublish

Résumé

Patient registries are a very important and essential tool for investigating rare diseases, as most physicians only see a limited number of cases during their career. Diseases of multi-organ autoimmunity and autoinflammation are especially challenging, as they are characterized by diverse clinical phenotypes and highly variable expressivity. The GAIN consortium (German multi-organ Auto Immunity Network) developed a dataset addressing these challenges. ICD-11, HPO, and ATC codes were incorporated to document various clinical manifestations and medications with a defined terminology. The GAIN dataset comprises detailed information on genetics, phenotypes, medication, and laboratory values. Between November 2019 and July 2022, twelve centers from Europe have registered 419 patients with multi-organ autoimmunity or autoinflammation. The median age at onset of symptoms was 13 years (IQR 3-28) and the median delay from onset to diagnosis was 5 years (IQR 1-14). Of 354 (84.5%) patients who were genetically tested, 248 (59.2%) had a defined monogenetic cause. For 87 (20.8%) patients, no mutation was found and for 19 (4.5%), the result was pending. The most common gene affected was NFkB1 (48, 11.5%), and the second common was CTLA4 (40, 9.5%), both genetic patient groups being fostered by specific research projects within GAIN. The GAIN registry may serve as a valuable resource for research in the inborn error of immunity community by providing a platform for etiological and diagnostic research projects, as well as observational trials on treatment options.

Identifiants

pubmed: 37084016
doi: 10.1007/s10875-023-01472-0
pii: 10.1007/s10875-023-01472-0
pmc: PMC10119522
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1289-1301

Informations de copyright

© 2023. The Author(s).

Références

Scheible R, Rusch S, Guzman D, Mahlaoui N, Ehl S, Kindle G. The NEW ESID online database network. Bioinformatics. 2019;35:5367–9. https://doi.org/10.1093/bioinformatics/btz525 .
doi: 10.1093/bioinformatics/btz525 pubmed: 31263866
Lablans M, Borg A, Ückert F. A RESTful interface to pseudonymization services in modern web applications. BMC Med Inform Decis Mak. 2015;15:2. https://doi.org/10.1186/s12911-014-0123-5 .
doi: 10.1186/s12911-014-0123-5 pubmed: 25656224 pmcid: 4350982
Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity. J Allergy Clin Immunol Pract. 2019;7:1763–70. https://doi.org/10.1016/j.jaip.2019.02.004 .
doi: 10.1016/j.jaip.2019.02.004 pubmed: 30776527
WHO World Health Organization. International classification of diseases for mortality and morbidity statistics (11th Revision). 2018. https://icd.who.int/en . Accessed 29 Mar 2021
Orphanet: the online rare disease and orphan drug data base. Orphanet nomenclature of rare diseases. 1999. http://www.orpha.net . Accessed 16 Nov 2020
Köhler S, Gargano M, Matentzoglu N, Carmody LC, Lewis-Smith D, Vasilevsky NA, et al. The Human Phenotype Ontology in 2021. Nucleic Acids Res. 2021;49:D1207–17. https://doi.org/10.1093/nar/gkaa1043 .
doi: 10.1093/nar/gkaa1043 pubmed: 33264411
WHO Collaborating Centre for Drug Statistics Methodology. ATC classification index with DDDs. Oslo, Norway; 2018. 2019
EMA European Medicine Agency. Article 57 export of “Brand name” for EU authorised medicines. 2020
Lefter M, Vis JK, Vermaat M, den Dunnen JT, Taschner PEM, Laros JFJ. Next generation HGVS nomenclature checker. Bioinformatics. 2021; https://doi.org/10.1093/bioinformatics/btab051 .
Yates AD, Achuthan P, Akanni W, Allen J, Allen J, Alvarez-Jarreta J, et al. Ensembl 2020. Nucleic Acids Res. 2020;48:D682–8. https://doi.org/10.1093/nar/gkz966 .
doi: 10.1093/nar/gkz966 pubmed: 31691826
Bethesda (MD), National Library of Medicine (US), National Center for Biotechnology Information. National Center for Biotechnology Information (NCBI). 1988. https://www.ncbi.nlm.nih.gov/ . Accessed 8 Mar 2022
Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, et al. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022;42:1473–507. https://doi.org/10.1007/s10875-022-01289-3 .
doi: 10.1007/s10875-022-01289-3 pubmed: 35748970 pmcid: 9244088
Elsink K, van Montfrans JM, van Gijn ME, Blom M, van Hagen PM, Kuijpers TW, Frederix GW. Cost and impact of early diagnosis in primary immunodeficiency disease: a literature review. Clin Immunol. 2020;213:108359. https://doi.org/10.1016/j.clim.2020.108359 .
doi: 10.1016/j.clim.2020.108359 pubmed: 32035178
Joshi AY, Iyer VN, Hagan JB, St. Sauver JL, Boyce TG. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009;84:16–22. https://doi.org/10.4065/84.1.16 .
doi: 10.4065/84.1.16 pubmed: 19121249 pmcid: 2630110
Schubert D, Bode C, Kenefeck R, Hou TZ, Wing JB, Kennedy A, et al. Autosomal-dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med. 2014;20:1410–6. https://doi.org/10.1038/nm.3746 .
doi: 10.1038/nm.3746 pubmed: 25329329 pmcid: 4668597
Fliegauf M, Bryant VL, Frede N, Slade C, Woon S-T, Lehnert K, et al. Haploinsufficiency of the NF-κB1 subunit p50 in common variable immunodeficiency. Am J Hum Genet. 2015;97:389–403. https://doi.org/10.1016/j.ajhg.2015.07.008 .
doi: 10.1016/j.ajhg.2015.07.008 pubmed: 26279205 pmcid: 4564940
Shillitoe B, Bangs C, Guzman D, Gennery AR, Longhurst HJ, Slatter M, et al. The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017. Clin Exp Immunol. 2018;192:284–91. https://doi.org/10.1111/cei.13125 .
doi: 10.1111/cei.13125 pubmed: 29878323 pmcid: 5980391
Seidel MG, Tesch VK, Yang L, Hauck F, Horn AL, Smolle MA, et al. The Immune Deficiency and Dysregulation Activity (IDDA2.1 ‘Kaleidoscope’) score and other clinical measures in inborn errors of immunity. J Clin Immunol. 2022;42:484–98. https://doi.org/10.1007/s10875-021-01177-2 .
doi: 10.1007/s10875-021-01177-2 pubmed: 34797428
Gaggiano C, Vitale A, Tufan A, Ragab G, Aragona E, Wiesik-Szewczyk E, et al. The Autoinflammatory Diseases Alliance Registry of monogenic autoinflammatory diseases. Front Med (Lausanne). 2022;9:980679. https://doi.org/10.3389/fmed.2022.980679 .
doi: 10.3389/fmed.2022.980679 pubmed: 36160138 pmcid: 9500177
El-Helou SM, Biegner A-K, Bode S, Ehl SR, Heeg M, Maccari ME, et al. The German National Registry of Primary Immunodeficiencies (2012–2017). Front Immunol. 2019;10:1272. https://doi.org/10.3389/fimmu.2019.01272 .
doi: 10.3389/fimmu.2019.01272 pubmed: 31379802 pmcid: 6659583

Auteurs

Paulina Staus (P)

Division Methods in Clinical Epidemiology, Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany. paulina.staus@uniklinik-freiburg.de.
Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany. paulina.staus@uniklinik-freiburg.de.

Stephan Rusch (S)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.

Sabine El-Helou (S)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.
Department of Rheumatology and Immunology, Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hanover, Germany.

Gabriele Müller (G)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.

Máté Krausz (M)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.
Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.

Ulf Geisen (U)

Excellence Center for Inflammation Medicine, Clinic for Rheumatology and Clinical Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Andrés Caballero-Oteyza (A)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.
Department of Rheumatology and Immunology, Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hanover, Germany.

Renate Krüger (R)

Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Shahrzad Bakhtiar (S)

Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Hospital for Children and Adolescents, University Hospital, Goethe University, Frankfurt am Main, Germany.

Min Ae Lee-Kirsch (MA)

Department of Pediatrics, University Hospital and Medical Faculty Carl Gustav-Carus, Technische Universität Dresden, Dresden, Germany.

Maria Fasshauer (M)

Hospital for Children & Adolescents, St. Georg Hospital, Leipzig, Germany.
Academic Teaching Hospital of the University of Leipzig, Immunodeficiency Center Leipzig (IDCL), Leipzig, Germany.

Ulrich Baumann (U)

Department of Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hanover, Germany.

Bimba Franziska Hoyer (BF)

Excellence Center for Inflammation Medicine, Clinic for Rheumatology and Clinical Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

João Farela Neves (J)

Primary Immunodeficiencies Unit, Hospital Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE, Lisbon, Portugal.
CHRC, Comprehensive Health Research Centre, NOVA Medical School, NOVA University of Lisbon, Lisbon, Portugal.
CEDOC, Chronic Diseases Research Center, NOVA Medical School, NOVA University of Lisbon, Lisbon, Portugal.

Michael Borte (M)

Hospital for Children & Adolescents, St. Georg Hospital, Leipzig, Germany.
Academic Teaching Hospital of the University of Leipzig, Immunodeficiency Center Leipzig (IDCL), Leipzig, Germany.

Maria Carrabba (M)

Dipartimento di Medicina Interna, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UOS Malattie Rare, Milan, Italy.

Fabian Hauck (F)

Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, Ludwig Maximilians Universität München, Munich, Germany.

Stephan Ehl (S)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.

Peter Bader (P)

Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Hospital for Children and Adolescents, University Hospital, Goethe University, Frankfurt am Main, Germany.

Horst von Bernuth (H)

Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Immunology, Labor Berlin GmbH, Berlin, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.

Faranaz Atschekzei (F)

Department of Rheumatology and Immunology, Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hanover, Germany.

Mikko R J Seppänen (MRJ)

The Rare Disease and Pediatric Research Centers, Hospital for Children and Adolescents and Adult Immunodeficiency Unit, Inflammation Center, University of Helsinki and HUS Helsinki, University Hospital, Helsinki, Finland.

Klaus Warnatz (K)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.
Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Alexandra Nieters (A)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.

Gerhard Kindle (G)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany.

Bodo Grimbacher (B)

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Faculty of Medicine, Medical Center, University of Freiburg, Breisacher Str. 115, 79106, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.
Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.
DZIF - German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.
CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.
RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH