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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01272

The German National Registry of Primary Immunodeficiencies (2012-2017)

 Sabine M. El-Helou1*, Anika-Kerstin Biegner1,  Sebastian Bode1, 2,  Stephan R. Ehl1, 2,  Maximilian Heeg1, 2,  Maria Elena Maccari1, 2, Henrike Ritterbusch1, 2, Stephan Rusch1, 3,  Raphael Scheible1, 4,  Klaus Warnatz1,  Faranaz Atschekzei5, Renata Beider5,  Diana Ernst5, Stev Gerschmann5,  Alexandra Jablonka5, Gudrun Mielke5,  Reinhold E. Schmidt5, Gesine Schürmann5,  Georgios Sogkas5,  Ulrich H. Baumann6, Christian Klemann6,  Dorothee Viemann6, Horst v. Bernuth7,  Renate Krüger7, Leif G. Hanitsch8,  Carmen Scheibenbogen8, Kirsten Wittke9, Michael H. Albert10, Anna Eichinger10,  Fabian Hauck10,  Christoph Klein11, Anita Rack-Hoch10, Franz Michael Sollinger10, Anne Avila12, Michael Borte12,  Stephan Borte12, Maria Fasshauer12, Anja Hauenherm12, Nils Kellner12, Anna H. Müller12, Anett Ülzen12,  Peter Bader13,  Shahrzad Bakhtiar13,  Jae-Yun Lee13, Ursula Heß13,  Ralf Schubert13,  Sandra Woelke13,  Zielen Stefan13,  Sujal Ghosh14,  Hans-Juergen Laws14, Jennifer Neubert14, Prasad T. Oommen14,  Manfred Hoenig15,  Ansgar S. Schulz15, Sandra Steinmann15, Klaus Schwarz16, Gregor Dückers17, Beate Lamers17, Vanessa Langemeyer17,  Tim Niehues17, Sonu Shai17,  Dagmar Graf18, Carmen Müglich19,  Marc T. Schmalzing19, Eva C. Schwaneck19, Hans-Peter Tony19, Gabriele Haase20,  Johannes G. Liese20,  Henner Morbach20, Florian Segerer20,  Dirk Foell21, Antje Hellige21,  Helmut Wittkowski21, Katja Masjosthusmann22, Michael Mohr23, Linda Geberzahn24,  Christian M. Hedrich24, 25, Christiane Müller24,  Angela Rösen-Wolff24,  Joachim Roesler24, Antje Zimmermann24, Uta Behrends26,  Nikolaus Rieber26, 27, Uwe Schauer28,  Rupert Handgtretinger27, Ursula Holzer27, Jörg Henes29, Lothar Kanz29, Christoph Boesecke30, Jürgen K. Rockstroh30, Carolynne Schwarze-Zander30, Jan-Christian Wasmuth30,  Dagmar Dilloo31, Brigitte Hülsmann31, Stefan Schönberger31,  Stefan Schreiber32, Rainald Zeuner32, Tobias Ankermann33,  Philipp von Bismarck33,  Hans-Iko Huppertz34, Petra Kaiser-Labusch34, Johann Greil35, Donate Jakoby35, Andreas E. Kulozik35,  Markus Metzler36,  Nora Naumann-Bartsch36, Bettina Sobik36, Norbert Graf37, Sabine Heine37,  Robin Kobbe38,  Kai Lehmberg38, Ingo Müller38, Friedrich Herrmann39,  Gerd Horneff39, 40, Ariane Klein39, 40, Joachim Peitz39, Nadine Schmidt39, Stefan Bielack41, Ute Groß-Wieltsch41,  Carl Friedrich Classen42, Jessica Klasen42, Peter Deutz43, Dirk Kamitz43, Lisa Lassay43,  Klaus Tenbrock43, Norbert Wagner43, Benedikt Bernbeck44, Bastian Brummel44, Eusebia Lara-Villacanas44, Esther Münstermann44, Dominik T. Schneider44,  Nadine Tietsch44, Marco Westkemper44, Michael Weiß45,  Christof Kramm46, Ingrid Kühnle46, Silke Kullmann46,  Hermann Girschick47, Christof Specker48, Elisabeth Vinnemeier-Laubenthal48, Henriette Haenicke17, Claudia Schulz17, Lothar Schweigerer17, Thomas G. Müller49,  Martina Stiefel49, Bernd H. Belohradsky50, Veronika Soetedjo4,  Gerhard Kindle1, 3* and  Bodo Grimbacher1, 51, 52, 53*
  • 1Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Freiburg University Medical Center, Germany
  • 2Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Germany
  • 3Faculty of Medicine, University of Freiburg, Germany
  • 4Institute of Medical Biometry and Statistics, University Medical Center Freiburg, Germany
  • 5Department of Clinical Immunology and Rheumatology, Hannover Medical School, Germany
  • 6Department of Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Germany
  • 7Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité Medical University of Berlin, Germany
  • 8Institute Medical Immunology, Charité Universitätsmedizin Berlin, Germany
  • 9Charité Universitätsmedizin Berlin, Institute Medical Immunology, Germany
  • 10Department of Pediatric Hematology and Oncology, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Germany
  • 11Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-University Munich, Germany
  • 12St. Georg Hospital, Germany
  • 13Klinik für Kinder und Jugendmedizin, Universitätsklinikum Frankfurt, Germany
  • 14Department of Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Düsseldorf, Germany
  • 15Klinik für Pädiatrie, Medizinische Fakultät, Universität Ulm, Germany
  • 16Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Germany
  • 17Center for Paediatrics and Adolescent Medicine, Helios Hospital Krefeld, Germany
  • 18MVZ Dr. Reising-Ackermann und Kollegen, Germany
  • 19Other, Germany
  • 20Department of Pediatrics, University Hospital Würzburg, Germany
  • 21Department of Pediatric Rheumatology and Immunology, University Hospital Münster, Germany
  • 22Department of General Paediatrics, University Hospital Muenster, Germany
  • 23Department of Hematology, Oncology and Respiratory Medicine, University Hospital Muenster, Germany
  • 24Department of Pediatrics, University Hospital Carl Gustav Carus, Germany
  • 25Department of Women’s and Children’s Health, University of Liverpool, United Kingdom
  • 26Children's Hospital Munchen Schwabing, Germany
  • 27Department of Oncology/Haematology, University Children's Hospital Tübingen, Germany
  • 28Ruhr University Bochum, Germany
  • 29Department of Internal Medicine II, University Hospital Tübingen, University of Tübingen, Germany
  • 30Department of Internal Medicine I, University Hospital Bonn, Germany
  • 31Department of Paediatric Haematology and Oncology, Bonn University Hospital, Germany
  • 32Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Germany
  • 33Klinik für Kinder und Jugendmedizin I, Universitätsklinikum Schleswig-Holstein, Germany
  • 34Bremen-Mitte Clinic, Germany
  • 35Department of Pediatric Oncology, Hematology and Immunology and Hopp Children’s Tumor Center, University of Heidelberg, Germany
  • 36Department of Paediatrics and Adolescent Medicine, University Hospital Erlangen, Germany
  • 37Department of Pediatric Oncology and Hematology, Saarland University Hospital, Germany
  • 38Division for Pediatric Stem Cell Transplantation and Immunology, Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany
  • 39Department of Pediatrics, Asklepios Clinic Sankt Augustin, Germany
  • 40Department of Pediatric and Adolescents medicine, University Hospital Cologne, Germany
  • 41Center for Pediatric, Adolescent and Women’s Medicine, Stuttgart Clinic, Germany
  • 42Kinder- und Jugendklinik, Universitätsmedizin Rostock, Germany
  • 43University Hospital RWTH Aachen, Germany
  • 44Klinikum Dortmund, Germany
  • 45Children's Hospital Amsterdamer Straße, Germany
  • 46Department of Hematology and Medical Oncology, University Medical Center Göttingen, Germany
  • 47Vivantes Hospital, Germany
  • 48St. Josef Hospital Essen-Werden, Germany
  • 49Department for Pediatric Hematology and Oncology, University Hospital in Halle, Germany
  • 50German self-help Congenital immunodeficiencies e.V., Germany
  • 51DZIF – German Center for Infection Research, Satellite Center Freiburg, Germany
  • 52Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Germany
  • 53Hannover Medical School, Germany

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.

Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.

Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1 to 25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients had (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0 - 88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, only severe combined immunodeficiency (SCID) had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49 % of all patients received immunoglobulin G (IgG) substitution (70% - subcutaneous; 29% - intravenous; 1% - unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.

Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.

Keywords: registry for primary immunodeficiency , Primary immunodeficiency (PID), German PID-NET registry, Immune System, PID prevalence, Prevalance, European Society for Immunodeficiencies, IgG substitution therapy, CVID, ESID, HSCT in PID, HSCT = hematopoietic stem cell transplant, gene therapy in PID, clinical online database

Received: 20 Mar 2019; Accepted: 20 May 2019.

Edited by:

Waleed Al-Herz, Kuwait University, Kuwait

Reviewed by:

Antonio Condino-Neto, University of São Paulo, Brazil
Asghar Aghamohammadi, Tehran University of Medical Sciences, Iran  

Copyright: © 2019 El-Helou, Biegner, Bode, Ehl, Heeg, Maccari, Ritterbusch, Rusch, Scheible, Warnatz, Atschekzei, Beider, Ernst, Gerschmann, Jablonka, Mielke, Schmidt, Schürmann, Sogkas, Baumann, Klemann, Viemann, Bernuth, Krüger, Hanitsch, Scheibenbogen, Wittke, Albert, Eichinger, Hauck, Klein, Rack-Hoch, Sollinger, Avila, Borte, Borte, Fasshauer, Hauenherm, Kellner, Müller, Ülzen, Bader, Bakhtiar, Lee, Heß, Schubert, Woelke, Stefan, Ghosh, Laws, Neubert, Oommen, Hoenig, Schulz, Steinmann, Schwarz, Dückers, Lamers, Langemeyer, Niehues, Shai, Graf, Müglich, Schmalzing, Schwaneck, Tony, Haase, Liese, Morbach, Segerer, Foell, Hellige, Wittkowski, Masjosthusmann, Mohr, Geberzahn, Hedrich, Müller, Rösen-Wolff, Roesler, Zimmermann, Behrends, Rieber, Schauer, Handgtretinger, Holzer, Henes, Kanz, Boesecke, Rockstroh, Schwarze-Zander, Wasmuth, Dilloo, Hülsmann, Schönberger, Schreiber, Zeuner, Ankermann, von Bismarck, Huppertz, Kaiser-Labusch, Greil, Jakoby, Kulozik, Metzler, Naumann-Bartsch, Sobik, Graf, Heine, Kobbe, Lehmberg, Müller, Herrmann, Horneff, Klein, Peitz, Schmidt, Bielack, Groß-Wieltsch, Classen, Klasen, Deutz, Kamitz, Lassay, Tenbrock, Wagner, Bernbeck, Brummel, Lara-Villacanas, Münstermann, Schneider, Tietsch, Westkemper, Weiß, Kramm, Kühnle, Kullmann, Girschick, Specker, Vinnemeier-Laubenthal, Haenicke, Schulz, Schweigerer, Müller, Stiefel, Belohradsky, Soetedjo, Kindle and Grimbacher. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Ms. Sabine M. El-Helou, Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Freiburg University Medical Center, Freiburg, Germany, sabine.el-helou@uniklinik-freiburg.de
Dr. Gerhard Kindle, Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Freiburg University Medical Center, Freiburg, Germany, gerhard.kindle@uniklinik-freiburg.de
Prof. Bodo Grimbacher, Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Freiburg University Medical Center, Freiburg, Germany, bodo.grimbacher@uniklinik-freiburg.de