The Interplay Between Inborn Error of Immunity and Blood Disorders: Unravelling Immune Defects Behind Common Haematological Diseases
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Biological samples.
- Who it may be relevant to
- Registry conditions: Hematologic Diseases. Basic parameters: up to 25 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada, France, Italy, Spain, Sweden
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
The universe of Inborn errors of Immunity (IEI) is rapidly expanding: their clinical spectrum is not only characterised by infections but often includes haematological complications. Moreover, an increasing number of "IEI phenocopies" due to somatic mutations in specific cell types are progressively being unveiled and complicate the genetic plot of IEI, which are therefore not only caused by germline mutations. However, these aspects have never been studied by large prospective studies. This study aims to fill this gap by prospectively recruiting patients \<25 y/o with haematologic disorders that fall into one of the following 4 subgroups: autoimmune cytopenia (AICs), polyclonal lymphoproliferation (PL), monoclonal (malignant) lymphoproliferation (ML), bone marrow failure/myelodysplasia (BMF/MDS). Recruited subjects will undergo an extensive immunologic workup (extended immunophenotyping, cytokine and autoantibody dosage) together with genetic testing (NGS) to detect both germline and somatic variants. Bulk RNA sequencing will be performed either as functional validation of variants or to identify altered pathways in selected cases with inconclusive genetics. Patient advocacy organisations (PAOs) will be pivotal to assist patients' needs throughout the project and to raise awareness of predictive and yet unknown signs of IEI. The study involves recruitment a total of almost 700 children over a 3-year period. Considering recent studies on AICs and BMF/MDS, a global detection rate of 30% "hidden" IEI is expected, with higher rates in the AIC subgroup and lower ones for ML, given the complexity of lymphoma pathogenesis. New IEI candidate genes or new examples of IEI phenocopies are expected to be identified. The immunological workup should detect early disease biomarkers or currently unknown molecular signatures of specific disorders. These may increase the chance of identifying an IEI in a specific subgroup and promptly address the patient to a targeted treatment or to hematopoietic stem cell transplantation, avoiding late complications, increasing patients' survival, and abating the economic burden of the disease on healthcare services. Finally, involvement of PAOs may foster patients' knowledge about their condition, increasing their compliance to disease follow-up and treatment and ameliorating their quality of life.
Interventions
- Other Biological samples
Immunological Screening and Genetic analysis
Primary outcome measures
- Number of children and young adults with blood disorders with new or known germline and somatic mutations that cause or modify disease, either in the lymphoid or myeloid compartments. [Time frame: From enrollment to the end of analysis (36 months)]
Secondary outcome measures (1)
- Percentage of pediatric and adolescent-young adult patients with hematologic disorders with altered immunological profiles [Time frame: From enrollment to the end of analysis (36 months)]
Eligibility criteria
Inclusion criteria
- Patients age < 25 years
- Patients with diagnosed autoimmune cytopenias (AIC), polyclonal lymphoproliferation (PL), lymphoma (ML), bone marrow failure, and myelodysplastic syndrome (BMF/MDS) (see details below)
- Signed Informed Consent
Exclusion criteria
- Patients with Lymphoma secondary to HIV or transplant
- Patient with self-resolving or post-infective AICs
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Diagnostic
Study locations
Canada · 2 centers
- CHU Sainte-Justine — Montreal
- CHU Sainte-Justine — Montreal
Italy · 2 centers
- Meyer Children's Hospital IRCCS, Firenze — Florence
- University of Rome Tor Vergata — Rome
France · 1 center
- Institut Imagine — Paris
Spain · 1 center
- Vall d'Hebron Institut de Recerca — Barcelona
Sweden · 1 center
- Karolinska Institutet — Stockholm
Identifiers
NCT: NCT06857604 · IEI-Haem