Inborn errors of immunity: manifestation, treatment, and outcome – an ESID registry 1994-2024 report on 30,628 patients

Abstract The European Society for Immunodeficiencies patient registry (ESID-R), established in 1994, is one of the world’s largest databases on inborn errors of immunity (IEI). IEI are genetic disorders predisposing patients to infections, autoimmunity, inflammation, allergies and malignancies. Treatments include antimicrobial therapy, immunoglobulin replacement, immune modulation, stem cell transplantation and gene therapy. Data from 194 centers in 33 countries capture clinical manifestations and treatments from birth onward, with annually expected updates. This report reviews the ESID-R’s structure, data content, and impact. The registry includes 30,628 patient datasets (aged 0–97.9 years; median follow-up: 7.2 years; total 825,568.2 patient-years), with 13,550 cases in 15 sub-studies. It has produced 84 peer-reviewed publications (mean citation rate: 95). Findings include real-world observations of IEI diagnoses, genetic causes, clinical manifestations, treatments, and survival trends. The ESID-R fosters global collaboration, advancing IEI research and patient care. This report highlights the key role of the multi-national ESID-R, led by an independent medical society, in evidence-based discovery. Summary Worldwide, most patient registries for inborn errors of immunity are national, with limited geographical and temporal scope. This 30-year ESID registry analysis of 30,628 patients’ longitudinal datasets enables robust epidemiological studies on natural disease courses including diagnosis, treatment, and survival, supporting expanded newborn screening and future AI applications in IEI research. Competing Interest Statement MGS received advisory board honoraria from Pharming. MHA received research support, consulting fees, and speaker honoraria from Octapharma. GK, FC declare no conflict of interest. LRD KU Leuven receives research funding and advisory board honoraria for IM from CSL-Behring and Boehringer-Ingelheim. BS has received travel grants from Pharming, and speaker honoraria from Takeda. Funding Statement MGS was in part funded by the Styrian Children's Cancer Aid Foundation (Steirische Kinderkrebshilfe). MHA represents the PID stream of the European Reference Network for Rare Immunological and Autoimmune Diseases (ERN-RITA). CEREDIH thank colleagues 390 from Universite de Paris, Imagine Institute, Data Science Platform, INSERM UMR 1163, F-75015, Paris, France for their contribution in the interface between ESID-R and the CEREDIH registry. LDN is supported by the Division of Intramural Research, NIAID, NIH. IM is a senior clinical researcher at FWO Vlaanderen. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol, the patient informed consent template and the center data transfer agreement plus amendments thereof were approved by the IRB and the data protection officer at the Medical University of Freiburg, Germany (Albert-Ludwigs-University). A substantial amendment was approved by the Medical University of Graz, Austria (24-334 ex 11/12, IRB00002556) and implemented in 2024. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes ↵43 These authors jointly designed, coordinated, and supervised the study Conflict of interest statement at the end of the article. Font sizes of figures enlarged, interpretation of results reworded, confidence intervals added to survival estimations. Data Availability All data produced in the present work are contained in the manuscript.