title: Clinical picture and treatment of 2212 patients with common variable immunodeficiency.
abstract: BACKGROUND
  Common variable immunodeficiency (CVID) is an antibody deficiency with an equal sex distribution and a high variability in clinical presentation. The main features include respiratory tract infections and their associated complications, enteropathy, autoimmunity, and lymphoproliferative disorders.
  
  
  OBJECTIVE
  This study analyzes the clinical presentation, association between clinical features, and differences and effects of immunoglobulin treatment in Europe.
  
  
  METHODS
  Data on 2212 patients with CVID from 28 medical centers contributing to the European Society for Immunodeficiencies Database were analyzed retrospectively.
  
  
  RESULTS
  Early disease onset (<10 years) was very frequent in our cohort (33.7%), especially in male subjects (39.8%). Male subjects with early-onset CVID were more prone to pneumonia and less prone to other complications suggesting a distinct disease entity. The diagnostic delay of CVID ranges between 4 and 5 years in many countries and is particularly high in subjects with early-onset CVID. Enteropathy, autoimmunity, granulomas, and splenomegaly formed a set of interrelated features, whereas bronchiectasis was not associated with any other clinical feature. Patient survival in this cohort was associated with age at onset and age at diagnosis only. There were different treatment strategies in Europe, with considerable differences in immunoglobulin dosing, ranging from 130 up to 750 mg/kg/mo. Patients with very low trough levels of less than 4 g/L had poor clinical outcomes, whereas higher trough levels were associated with a reduced frequency of serious bacterial infections.
  
  
  CONCLUSIONS
  Patients with CVID are being managed differently throughout Europe, affecting various outcome measures. Clinically, CVID is a truly variable antibody deficiency syndrome.
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Centre Freiburg and University of Freiburg, Freiburg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gathmann
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service d'Immuno-Hématologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Paris, France, Assistance Publique-Hôpitaux de Paris, CEREDIH, Centre de Référence des Déficits Immunitaires Héréditaires, Hôpital Universitaire Necker-Enfants Malades, Paris, France, and Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, Paris, France.
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.affiliation: Department of Clinical Immunology, Hôpital Saint-Louis, AP-HP and Univ Paris Diderot, Sorbonne Paris Cité, EA3963, Paris, France, Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Paris, France, and the DEFI study group.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gérard
authors.affiliation: Department of Clinical Immunology, Hôpital Saint-Louis, AP-HP and Univ Paris Diderot, Sorbonne Paris Cité, EA3963, Paris, France, Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Paris, France, and the DEFI study group.
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Centre Freiburg and University of Freiburg, Freiburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Centre Freiburg and University of Freiburg, Freiburg, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Schulze
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Centre Freiburg and University of Freiburg, Freiburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kindle
authors.affiliation: Dutch Working Party for Immunodeficiencies (WID), Amsterdam, The Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.affiliation: Medical Department Sanquin Blood Supply Foundation, Amsterdam, The Netherlands.
authors.forename: Rachel T
authors.initials: RT
authors.lastname: van Beem
authors.affiliation: UCL Medical School Royal Free Campus and Royal Free Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Guzman
authors.affiliation: UCL Medical School Royal Free Campus and Royal Free Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Sarita
authors.initials: S
authors.lastname: Workman
authors.affiliation: Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall d'Hebron Research Institute, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Soler-Palacín
authors.affiliation: Department of Pneumology, Hospital Universitari Vall d'Hebron, UAB, CIBER Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: De Gracia
authors.affiliation: Clinic for Immunology and Rheumatology, Medical University Hannover, Hannover, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.affiliation: Clinic for Immunology and Rheumatology, Medical University Hannover, Hannover, Germany.
authors.forename: Reinhold E
authors.initials: RE
authors.lastname: Schmidt
authors.affiliation: Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University and St Anne's University Hospital, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Litzman
authors.affiliation: St Anne's University Hospital, Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Hlavackova
authors.affiliation: Department of Clinical Immunology and Allergy, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Thon
authors.affiliation: Children's Hospital, Municipal Hospital "St Georg," Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Borte
authors.affiliation: Children's Hospital, Municipal Hospital "St Georg," Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany; Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Borte
authors.affiliation: Department of Clinical Biochemistry and Immunology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: Dinakantha
authors.initials: D
authors.lastname: Kumararatne
authors.affiliation: Department of Immunology, St James's Hospital Dublin and Trinity College Dublin, Dublin, Ireland.
authors.forename: Conleth
authors.initials: C
authors.lastname: Feighery
authors.affiliation: Department of Immunology, Barts Health NHS Trust, London, United Kingdom.
authors.forename: Hilary
authors.initials: H
authors.lastname: Longhurst
authors.affiliation: Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Helbert
authors.affiliation: Children University Hospital, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Szaflarska
authors.affiliation: Department of Immunology, 2nd School of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Sediva
authors.affiliation: Dr v. Haunersches Kinderspital, Ludwig Maximilians University, Munich, Germany.
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Belohradsky
authors.affiliation: Institute of Child Health/Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Jones
authors.affiliation: Immunology Unit, Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.affiliation: Department of Pediatrics, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meyts
authors.affiliation: Department of Pediatric Immunology, Ege University Faculty of Medicine, Izmir, Turkey.
authors.forename: Necil
authors.initials: N
authors.lastname: Kutukculer
authors.affiliation: Department of Infectious Diseases, County Hospital Ryhov Jönköping, Jönköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Wågström
authors.affiliation: Primary Immunodeficiency Clinic, Department of Pediatrics, Cairo University, Cairo, Egypt.
authors.forename: Nermeen Mouftah
authors.initials: NM
authors.lastname: Galal
authors.affiliation: Department of Pediatrics, University Hospital Dresden, Dresden, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Roesler
authors.affiliation: Pediatric Immunology and Rheumatology Referral Centre, First Department of Pediatrics, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Farmaki
authors.affiliation: Research and Clinical Centre for Pediatric Hematology, Oncology, Immunology, Moscow, Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Zinovieva
authors.affiliation: 1st Pediatric Department, Faculty of Medicine, Comenius University and Children University Hospital, Bratislava, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Ciznar
authors.affiliation: Aristotle University of Thessaloniki, Fourth Department of Pediatrics, Papageorgiou Hospital, Thessaloniki, Greece.
authors.forename: Efimia
authors.initials: E
authors.lastname: Papadopoulou-Alataki
authors.affiliation: Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bienemann
authors.affiliation: Tallinn Children's Hospital, Tallinn, Estonia.
authors.forename: Sirje
authors.initials: S
authors.lastname: Velbri
authors.affiliation: Medical Science Department, CSL Behring, West Sussex, United Kingdom.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Panahloo
authors.affiliation: Center for Chronic Immunodeficiency (CCI), University Medical Centre Freiburg and University of Freiburg, Freiburg, Germany; UCL Medical School Royal Free Campus and Royal Free Hospital NHS Foundation Trust, London, United Kingdom. Electronic address: bodo.grimbacher@uniklinik-freiburg.de.
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015551:Autoimmunity; D001987:Bronchiectasis / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D057210:Delayed Diagnosis; D005060:Europe; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008232:Lymphoproliferative Disorders / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D008297:Male; D011014:Pneumonia / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D012189:Retrospective Studies; D013163:Splenomegaly / Q000473:pathology; D016019:Survival Analysis
chemical_list: D016756:Immunoglobulins, Intravenous
keywords: Common variable immunodeficiency; autoimmunity; enteropathy; granulomas; immunoglobulin replacement; lymphadenopathy; patient self-reported outcomes; primary antibody deficiency; quality of life; treatment