INTRODUCTION
Immune cytopenias are disorders characterized by immune-mediated destruction of hematopoietic cell lineages. The most common form in children is immune thrombocytopenia (ITP), followed by autoimmune hemolytic anemia (AIHA) and autoimmune neutropenia (AIN)1. In children affected by AIHA, a link between immune cytopenias and IEI was observed in 8-10% of cases2. In a pediatric cohort with Evans syndrome (ES), defined as synchronous or metachronous association between AIHA and ITP, immune-dysregulation phenomena, including IEI, were found in 70% of the patients3,4.
IEI are congenital disorders caused by defects in genes involved in the development, function and regulation of the immune system, resulting not only in increased susceptibility to infections, but also in inflammatory, autoimmune, allergic, non-malignant lymphoproliferative and neoplastic manifestations5–7. IEI most frequently associated with immune cytopenias are: Common variable immune deficiency (CVID), Autoimmune lymphoproliferative syndrome (ALPS), Wiskott-Aldrich syndrome and Combined immunodeficiency (CID)5. Depending on the different forms of IEI, the pathogenic mechanisms of cytopenias identified thus far are various: humoral and cell-mediated adaptive immunity8, immune-dysregulation in form of hemophagocytosis and splenic sequestration secondary to abnormal lymphoproliferation6,9, myelodysplasia10, primary bone marrow failure and myelosuppression secondary to infections, malignancies and bone marrow lymphocytic infiltration5. IEI-related immune cytopenias differ from idiopathic forms on these issues: late onset, multi-lineage involvement, chronic/relapsing course and tendency towards treatment refractoriness1. Aim of this study was to assess prevalence and clinical/immunological predictive factors of IEI in children with immune cytopenias, identifying patients worthy of IEI-related molecular analysis.