Review and Feature Article
The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity

https://doi.org/10.1016/j.jaip.2019.02.004Get rights and content

Patient registries are instrumental for clinical research in rare diseases. They help to achieve a sufficient sample size for epidemiological and clinical research and to assess the feasibility of clinical trials. The European Society for Immunodeficiencies (ESID) registry currently comprises information on more than 25,000 patients with inborn errors of immunity (IEI). The prerequisite of a patient to be included into the ESID registry is an IEI either defined by a defect in a gene included in the disease classification of the international union of immunological societies, or verified by applying clinical criteria. Because a relevant number of patients, including those with common variable immunodeficiency (CVID), representing the largest group of patients in the registry, remain without a genetic diagnosis, consensus on classification of these patients is mandatory. Here, we present clinical criteria for a large number of IEI that were designed in expert panels with an external review. They were implemented for novel entries and verification of existing data sets from 2014, yielding a substantial refinement. For instance, 8% of adults and 27% of children with CVID (176 of 1704 patients) were reclassified to 22 different immunodeficiencies, illustrating progress in genetics, but also the previous lack of standardized disease definitions. Importantly, apart from registry purposes, the clinical criteria are also helpful to support treatment decisions in the absence of a genetic diagnosis or in patients with variants of unknown significance.

Section snippets

Materials and Methods

For each of 92 clinical IEI entities to be verified or excluded in patients who lack a genetic diagnosis, a number of mandatory and suggestive clinical features were defined by international experts and collected between 2013 and 2018. Drafts of proposed criteria were elaborated by experts in the field and were subsequently peer reviewed by 1 or more external experts in the respective category of IEI before implementation. Contributors and reviewers of each entity are stated. A regular quality

Results: Clinical Diagnosis Criteria For Iei And Their Application

The document titled “ESID Registry—Working Definitions for Clinical Diagnosis of PID/IEI” is available in the Online Repository of this article (see Table E1 in this article's Online Repository at www.jaci-inpractice.org) and, in a regularly updated version, on the ESID website.20 Recently, each diagnosis of the compilation was supplemented with OMIM (Online Mendelian Inheritance in Man) numbers of corresponding, genetically defined, diagnosis entities if available, and the respective category

Discussion

The present document describes the development and current version of the ESID Registry Working Definitions for Clinical Diagnosis of PID/IEI as of January 2019, and comprises the entire spectrum of primary immunodeficiencies covered by the ESID registry to date. As it uses clinical disease definitions rather than separate genetic defects, this list may appear shorter than those provided in the IUIS documents. The document was designed to enable correct classification of patients without the

Acknowledgments

The authors would like to thank PPTA (https://www.pptaglobal.org) and its member companies for financial support of the ESID registry.

ESID Registry Working Party members and collaborators are as follows: Mario Abinun, Michael Albert, Sarah Beaussant Cohen, Jacinta Bustamante, Andrew Cant, Jean-Laurent Casanova, Helen Chapel, Genevieve de Saint Basile, Esther de Vries, Inderjeet Dokal, Jean Donadieu, Anne Durandy, David Edgar, Teresa Espanol, Amos Etzioni, Alain Fischer, Bobby Gaspar, Richard

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Conflicts of interest: M.G.S. is in part funded by the Styrian Children’s Cancer Aid (Steirische Kinderkrebshilfe) Foundation. S.E. acknowledges support by the Bundeministerium für Bildung und Forschung (BMBF) (01EO1303) and the Deutsche Forschungsgemeinschaft (DFG) (Eh145/9-1 EURO-CID). G.K., R.S., and S.R. acknowledge support by the BMBF (BMBF 01GM0896, 01GM1111B, 01GM1517C, and 01EO1303). B.G. is supported by the German Research Foundation (DFG) under Germany's Excellence Strategy (CIBSS – EXC-2189 – Project ID 390939984) and through the Cluster of Excellence RESIST (EXC 2155; Project ID A2). The rest of the authors declare that they have no relevant conflicts of interest.

These authors contributed equally to this work.

These authors jointly coordinated and supervised this work.

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