Translational and clinical immunologyInitial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations
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Patients
As of March 2019, 21,485 patients of 68 nationalities were documented by 29 countries participating in the ESID Registry based on informed consent (No. 493/14 of the Ethical Committee Freiburg). From these, the following were excluded: 161 patients without an IEI diagnosis and 304 patients with “unclassified immunodeficiency,” because there was concern whether these patients indeed represent patients with IEI, or rather secondary immunodeficiencies or other diseases. Another 3362 patients were
Infection is the most frequent initial presenting manifestation of IEI
Of 16,486 patients with IEI documented in the ESID Registry and eligible for this study, 12,741 (77%) initially presented with infection, 2,955 (18%) with immune dysregulation, 1,983 (12%) with syndromic features, and 137 (0.8%) with malignancy (Fig 2). A total of 1292 (8%) presented with “other” symptoms (including, eg, aphthae, asthma, alopecia, fatigue, and ataxia), with 254 of them (1.5% of all patients) as the only initial manifestation. Abnormal laboratory test results (eg,
Discussion
Here, we report the age-related presenting manifestations of IEI in general and in different IEI disease groups across a cohort of 16,574 patients documented in the ESID Registry. Our results emphasize the importance of both immune dysregulation and syndromic features (18% and 12% of all patients, respectively) in addition to infections as the initial manifestation of IEI. A third of patients (33%) showed initial manifestation of their IEI within the first year of life and another third (30%)
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The European Society for Immunodeficiencies Registry was supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung [BMBF] grant nos. 01GM0896, 01GM1111B, 01GM1517C, 01EO1303, and 01ZZ1801B), the European Union (grant no. HEALTH-F2-2008-201549 [EURO-PADnet]), the pharmaceutical companies Novartis, GlaxoSmithKline, LFB, UCB UK, and Pharming, the Plasma Protein Therapeutics Association, the Care-for-Rare Foundation, PROimmune e.V., ERN RITA, and the European Society for Immunodeficiencies (www.ESID.org).
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
Data sharing: Deidentified patient data collected for this study are available to others with publication of this article according to the European Society for Immunodeficiencies Registry data access and publication rules (https://esid.org/Education/Call-for-studies/Data-access-and-Publication-rules-Research-Proposal-Form).
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These authors contributed equally to this work.
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For a complete list of European Society for Immunodeficiencies Registry Working Party collaborators, please see the Acknowledgment section at the end of the article.