Immune deficiencies, infection, and systemic immune disorders
Clinical picture and treatment of 2212 patients with common variable immunodeficiency

https://doi.org/10.1016/j.jaci.2013.12.1077Get rights and content

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.

Conclusion

Patients with CVID are being managed differently throughout Europe, affecting various outcome measures. Clinically, CVID is a truly variable antibody deficiency syndrome.

Section snippets

Methods

We analyzed data on 2212 patients with a confirmed diagnosis of CVID reported in the ESID Database. We chose to use the ESID registry as a resource for this study because it provides us with longitudinal data for a large cohort of patients. The disadvantage of this approach is that the data are not as completely documented and reviewed as in a clinical trial. The primary source for the data is the patient’s file. Data are often entered by research assistants and not physicians, which means that

Results

We analyzed data on 2212 patients. At the time of analysis (October 23, 2012), 2010 patients were reported to be alive, whereas 124 were deceased, and 78 had been lost to follow-up. One thousand one hundred thirty-one (51.1%) patients were female, and 1081 (48.9%) patients were male. Of the living patients, 129 (6.4%) were younger than age 12 years, 139 (6.9%) were between 12 and 17 years old, and 1742 (86.7%) were 18 years and older. The overall ratio between female and male patients was

Discussion

First of all, we must caution that our results reflect clinical observations and measures and must be distinguished from a controlled clinical trial. Some of the variables in our analysis represent “soft” data, such as the date of onset, as well as patient-reported health outcomes. In addition, centers apply different methods to diagnose findings, such as enteropathy and bronchiectasis. This might explain, at least in part, the differences in the frequency of single features between centers.

References (22)

  • R. Micol et al.

    Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia

    J Allergy Clin Immunol

    (2012)

    • Cited by (0)

    The European Society for Immunodeficiencies Database is sponsored by PPTA Europe (http://www.pptaglobal.org). CSL Behring UK provided support for this study by financing the statistical evaluation at Meridian HealthComms. This study was supported by the German Federal Ministry of Education and Research (BMBF 01 EO 0803) and the DZIF project TTU 04.802. Finally, the study was supported by EU grant HEALTH-F2-2008-201549 (EURO-PADnet). Sabine El-Helou entered data in some of the German centers. Her position was funded by German BMBF grant 01GM0896 (PID-NET). D.K. (Cambridge) was supported by National Institute of Health Research of the UK, Cambridge Biomedical Centre. Great Ormond Street Hospital Children's Charity part funded the post of Zoe Allwood's, who entered data at Great Ormond Street Hospital. S.B. was supported by funds from the German Federal Ministry of Education and Research (BMBF 1315883). T.W. and R.E.S. were funded by grant DZIF TTU-IICH 07.801: Genetic susceptibility and biomarkers of infection control. P.C. thanks the Jeffrey Modell Foundation for financial grant for support of the PID Register and Slovak National PID Database. The Dutch National Registry is supported by an unrestricted grant from Sanquin Blood Supply Foundation, Amsterdam, The Netherlands. CEREDIH is funded by the French Ministry of Health, and had received additional support from the French association of patients with PID (IRIS). CEREDIH receives educational grants from LFB, Baxter Biosciences, CSL Behring, Octapharma, Pfizer, Orphan Europe, and the Binding Site.

    Disclosure of potential conflict of interest: B. Gathmann has received research support from the European Commission, has received fees for participation in review activities from PPTA, has received administrative support for statistical analysis from CSL Behring UK, and has received travel support from CSL Behring UK. E. Oksenhendler has provided expert testimony on behalf of CSL Behring and has received payment for lectures from CSL Behring and Grifols. K. Warnatz has received research support from the Federal Ministry of Education and Research and the German Research Foundation; has received payment for lectures from Baxter, GlaxoSmithKline, CSL Behring, Pfizer, the American Academy of Allergy, Asthma & Immunology, Biotest, and Novartis Pharma; and has received payment for manuscript preparation from UCB Pharma. I. Schulze has received payment for lectures from the German Society of Pediatrics and Adolescent Medicine. G. Kindle has received research support from PPTA and is employed by University Medical Center Freiburg. S. Workman has received a consulting fee from Octapharma and has received travel support from Octapharma, Grifols, CSL Behring, Biotest, Baxter, BPL, and Viropharma. P. Soler Palacin has consultant arrangements with CSL Behring, has provided expert testimony on behalf of CSL Behring, has received research support from CSL Behring and Baxter, has received payment for lectures from CSL Behring, and has received travel support from CSL Behring and Baxter. J. Litzman is on the HyQvia advisory board for Baxter Healthcare Corporate and has received payment for lectures from Biotest. D. Kumararatne has consultant arrangements with Novartis, is employed by Cambridge University Hospital, has received research support from the National Institute of Medical Research of the United Kingdom through Cambridge Biomedical Centre, and has received travel support from CSL Behring and Thermo Fisher. H. Longhurst has received research support from LFB and CSL Behring; has received consulting fees from CSL Behring and Baxter; has received travel support, fees for participation in review activities, and payment for lectures from CSL Behring; has received payment for writing or reviewing this manuscript and provision of writing assistance, medicines, equipment, or administrative support from HAE UK; and has received payment for development of educational presentations from Viropharma, CSL Behring, and Shire. M. Helbert has received payment for lectures from CSL Behring, Octapharma, Bio Products Laboratory, and Grifols and has received travel support from CSL Behring, Octapharma, and Bio Products Laboratory. A. Sediva has received general support from the Jeffrey Model Foundation. A. Jones has received payment for lectures from CSL Behring and has received travel support from CSL Behring. U. Baumann has received grants from the European Union and EURO-PADnet, has received payment for lectures from Baxter and CLS Behring, and has received travel support from Octapharma. B. Grimbacher has received research support from the Federal Ministry of Education and Research; receives royalties from Springer; and has received travel support from CSL Behring, the American Academy of Allergy, Asthma & Immunology, the Japanese Society for Immunodeficiencies, the European Society for Immunodeficiencies, the Latin American Society for Immunodeficiencies, and the Primary Immunodeficiencies Meeting. The rest of the authors declare that they have no relevant conflicts of interest.

    ‡

    WID collaborators list

    Dutch Inter University Working party for the Study of Immune deficiencies (WID) collaborators (all MDs):

    R. J. M. ten Berge (AMC), T. W. Kuijpers (AMC), E. de Vries (JBZ), M. Bijl (UMCG), E. H. Scholvink (UMCG), J. T. van Dissel (LUMC), R. G. M. Bredius (LUMC), M. H. Haverkamp (LUMC), A. Warris (UMCN), A. Simon (UMCN), V. A. S. H. Dalm (ErasmusMC), G. J. A. Driessen (ErasmusMC), P. Ellerbroek (UMCU), J. M. van Montfrans (UMCU), J. L. Maarschalk-Ellerbroek (UMCU), J. W. M. van der Meer (UMCN), M. van Deuren (UMCN), M. G. Netea (UMCN), F. Veerdonk (UMCN)

    ∗

    CEREDIH collaborators list

    CEREDIH (Centre de Référence Déficits Immunitaires Héréditaires) collaborators:

    Clinical Research Associates: Nathalie de Vergnes, Laurence Costes, Chantal Andriamanga, Virginie Courteille and Pauline Brosselin.

    MDs: Nizar Mahlaoui, Anne-Sophie Korganow, Patrick Lutz, Jean-Louis Pasquali, Nathalie Aladjidi, Yves Perel, Jean-François Viallard, Bernard Bonnotte, Claire Briandet, Gérard Couillault, Faézeh Legrand, Pierre-Simon Rohrlich, Virginie Gandemer, Bernard Grosbois, Philippe Lemoine, Laurent Aaron, Cyrille Hoarau, Yvon Lebranchu, Rolland Jaussaud, Martine Munzer, Aude Marie-Cardine, Jean-Pierre Vannier, Serge Jacquot, François Tron, Claire Fieschi, Lionel Galicier, Marion Malphettes, Guy Leverger, Emilie Catherinot, Hélène Coignard-Biehler, Olivia Chandesris, Stéphane Blanche, Jean-Laurent Casanova, Marianne Debré, Pierre Frange, Despina Moshous, Bénédicte Neven, Luc Mouthon, Olivier Lambotte, Yves Levy, Frédéric Bernard, Eric Jeziorski, Alain Le Quellec, Vincent Le Moing, Arnaud Jaccard, Christophe Piguet, Pierre Bordigoni, Alexandra Salmon, Fanny Fouyssac, Daniel Adoue, Philippe Arlet, Hervé Rubie, Eric Hachulla, David Launay, Françoise Mazingue, Vincent Barlogis, Gérard Michel, Nicolas Schleinitz, Anne Deville, Fabienne Dulieu, Fabrice Monpoux, Martine Gardembas, Isabelle Pellier, Boris Bienvenu, Patrick Boutard, Mohamed Hamidou, Agathe Masseau, Caroline Thomas, Kaïss Lassoued, Jean-Pierre Marolleau, Bruno Royer, Frédéric Millot, François Demeocq, Christian Massot, Françoise Sarrot-Reynauld, Dominique Plantaz, Yves Bertrand, Kamila Kebaili, Grégoire Cozon, Isabelle Durieu, Raphaëlle Nove-Josserand, Michel Pavic, Jean-Louis Stephan, Jean Donadieu, Paul Landais, Marc Lecuit, Capucine Picard, Felipe Suarez, Olivier Lortholary, Eric Oksenhendler, Olivier Hermine, Alain Fischer.

    View full text
    Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.