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.