Inborn errors of immunity (IEI) are a group of rare disorders displaying infections and also haematological autoimmunity and malignancy, which strongly impact on patients’ life expectancy and quality of life. Recently, inherited bone marrow failure syndromes (BMFS) have been categorised among IEI and somatic mutations leading to IEI-phenocopies have been detected. Yet, extensive prospective studies addressed at unveiling IEI among haematological manifestations are lacking.

Our research aims at revealing IEI behind blood disorders of children and young adults, detecting early disease biomarkers that may lead to an appropriate treatment and improve patients’ outcome and quality of life.

In this international study, we will enrol patients <25 y/o with autoimmune cytopenia, polyclonal and clonal lymphoproliferation, myelodysplasia and BMFS. Recruited subjects will undergo an extensive immunologic workup 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. PAOs will be pivotal to assist patients’ needs throughout the project and to raise awareness of predictive and yet unknown signs of IEI.

Results will allow us to assess the frequency of IEI behind common blood disorders, increasing collaboration between immunologists and haematologists. We also aim to identify molecular biomarkers that may foster an early diagnosis and guide treatment decisions to ameliorate patients’ life expectancy and quality of life.