Research Studies

Information on ongoing studies using the ESID Registry Database.

For completed studies please refer to the list of Registry publications.

If you want to propose a study to the ESID Registry, please use the following Research Proposal Form:

ESID _Research proposal form Oct21.2025

ESID Registry Study Project Fees | Reimbursement Scheme as of August 2023

Please be aware that there will be a calculation of costs to be reimbursed by the study center to ESID for non-routine additional technical and administrative work according to a template that will be subject to adaptation and changes without prior notice.

Publication Rules 2.1 for the ESID registry Nov29.2022fin

Study Levels

All ESID Registry sub-studies must comply with the quality and type of non-interventional observational clinical and laboratory data collection by chart review as outlined in the ESID Registry main study protocol (latest version 3.0 as of June 2024, available to all participants). ESID Registry sub-studies may be categorized into three levels:

Level 1 (baseline, simple epidemiology): baseline registry data export analyses of already existing (routinely captured) data for, e.g., cross-sectional epidemiological studies or to locate patients with ultrarare diseases for add-on studies. If retrospective longitudinal data are needed (field histories), these will need to be provided by Castor-edc on a designated service order. Example: Initial manifestations of IEI.
Level 2 (add-on, e.g., limited longitudinal data capture): Sub-studies typically limited to specific disease categories, diagnoses, or geographically, with an add-on CRF (either in Castor-edc or hybrid), often prospective disease-specific data collections or surveys. Example: HLH-Registry.
Level 3 (add-on, separate study protocol-based prospective observational study): Larger sub-studies with a clear study endpoint and duration, limited to specific, mostly monogenically defined diseases; often pharma-sponsored. New: may also be designed to serve as registry-based post-authorization efficacy and safety (PAES) study. Example: APDS Study.

Evaluation of Study Proposals

Each submitted study proposal is first reviewed by the Registry Chairperson to ensure completeness, after which it is forwarded to the Steering Committee (SC; see the Registry Working Party main page) for evaluation. The SC is composed of six experts in the field of IEI/PID and clinical research from diverse countries and professional backgrounds, together with the Chairperson. The committee meets regularly and aims to provide feedback within 2–4 weeks of submission.

The primary purpose of the review is to assess proposals for potential redundancies—helping to prevent duplicate or overlapping studies within the ESID registry—and to evaluate the overall feasibility of the proposed project. Please note that the SC does not assess the scientific merit or novelty of the study idea itself, and that responsibility for defining the study scope, ensuring proper conduct, and maintaining ethical and legal compliance with the ESID registry protocol rests entirely with the study’s principal investigator or research group.

Before developing a detailed study proposal, we strongly encourage applicants to review the ESID Level 1 (baseline) dataset. It is also important to be aware that data from the annually recommended patient follow-up visits may not always be complete or up to date.

GAIN2 – Genetic autoimmune network

The GAIN2_ESID-level-2 dataset has been developed for the documentation of patients with both, immunodeficiency and immune dysregulation, i.e. autoimmuniy and/or autoinflammation. Hence, the GAIN2_ESID-level-2 dataset shall facilitate the publication of patient cohorts with multi-organ autoimmunity and autoinflammation. This dataset is now available on the ESID-Castor database.

Monoallelic LIG4 mutations in combined immunodeficiency

We would like to invite you to participate in an ESID-supported study on monoallelic LIG4-dependent combined immunodeficiency. If your centre follows patients with monoallelic LIG4 variants and you are interested in participating, please contact: salome.stein@unibas.ch and cc: mike.recher@usb.ch. A case report form will be provided upon expression of interest.

Genotype-phenotype correlation and precise phenotypic analysis utilizing medical ontologies in defined cohorts from the ESID registry: level 2 data for SOCS1 and APDS

The Human Phenotype Ontology (HPO) and GA4GH Phenopacket Schema provide a machine-readable framework for encoding clinical phenotypes based on semantic similarity scoring across individuals. This may perspectively allow for longitudinal modelling and outcome prediction using modern machine learning methods. This study will test the feasibility and analytical value using proof-of-principle cohorts (SOCS1 haploinsufficiency and APDS).

SOCS1 level 3 Registry Study

The team aims to provide a longitudinal data collection/registry for SOCS1 deficient patients for better understanding of the natural history, rare disease manifestations (e.g. mycobacterial disease), distribution of variants, clinical penetrance of the variants among families, treatment efficacy (JAKi, other immunosuppressors, as well outcomes from HSCT and long term prognosis (e.g. lymphomagenesis). Provision of data for the study will be available through a CRF on the ESID Registry soon.

Use of immune modifying drugs in IEI/PID across Europe

The objectives of this study are to present epidemiologically descriptive statistical summary of the use of immune modifying drugs in IEI/PID in Europe, estimation of the quantity and variety of used drugs and review which drugs in which IEI/PID, use linked to organ manifestations, targeted/off-target (gene pathway), economical factors.

Pediatric CVID – does it exist?

The primary objectives of this study are to compare the genetic background of pediatric and adult CVID patients, including differences across defined age subgroups (25 years) and also to evaluate whether monogenic CVID is more frequent in pediatric cases.

ZNFX1 - Collaborative Study

We would like to kindly invite you to participate in a collaborative effort to identify patients with ZNFX1 deficiency. We are collecting clinical, immunological and transplant data on patients with ZNFX1 deficiency. ZNFX1 deficiency has been described by independent groups, with initial reports emphasizing either susceptibility to mycobacterial disease or a multisystem inflammatory phenotype with viral susceptibility and immune dysregulation (e.g., Vavassori et al., J Allergy Clin Immunol 2021). Our aim is to capture the full range of presentations, treatments, and outcomes across centers.

STAT6GOF - Clinical cohort Study

Contribute to the STAT6GOF international consortium As you likely know, STAT6 gain-of-function (STAT6GOF) disease is a relatively recently described inborn error of immunity that presents with severe allergic inflammation. ESID just launched a Collaborative Clinical Cohort Study on STAT6GOF disease.The goal of the study is to define the natural history and treatment outcomes of this new inborn error of immunity. Only few patients have been registered in the ESID registry so far, so this is a public call to see if others may have cases to contribute, and if you would like to join our consortium to combine resources....

HSCT indications and outcome of HSCT for Ras-Associated Autoimmune Leukoproliferative Disorder (RALD), a joint ESID/ EBMT IEWP study

An joint ESID-EBMT study to capture the data on RAS associated Lymphoproliferative Disorder (RALD) outcomes post HSCT. The group is interested in knowing more about the less well understood characteristics of this orphan disease and would like to extend this study to RALD patients who have not had a transplant and managed otherwise and we have contacted the ESID registry. This study, we feel, will significantly enhance our understanding of this disease better, to better delineate the sub-population who might benefit from HSCT and to look into appropriate conditioning/ donor source, to identify unique complications of the transplant and get a better idea on outcomes of such a transplant.

Evaluation of immune reconstitution of patients with adenosine deaminase deficiency treated with enzyme replacement therapy a joint ESID-IEWP study

The study is currently in progress. The aim is to carry out a multicentre research project to evaluate the level of immune reconstitution achieved by patients with ADA-SCID on ERT while awaiting a more definitive treatment with HSCT or GT. Because GT is now recommended over HSCT if there is no matched sibling donor, but it is associated with a significantly longer waiting time, precise knowledge about timing of immune reconstitution, and when to consider treatment failure and plan an „urgent“ HSCT is important in the management of patients with ADA-SCID.

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Chairperson WP Registry (2022-2026)

Prof. Markus G. Seidel

Phone: +43 316 385 80215

E-mail: registry@esid.org