Immunophenotype identifies children with immune cytopenias at risk of
inborn errors of immunity-related mutations
Abstract
Background Immune thrombocytopenia (ITP), autoimmune hemolytic
anemia (AIHA) and autoimmune neutropenia (AIN) are disorders
characterized by immune-mediated destruction of hematopoietic cell
lineages. A link between pediatric immune cytopenias and inborn errors
of immunity (IEI) was established in particular in the combined and
chronic forms. Objective Identification of predictive factors
of IEI in immune cytopenic children is an important objective for a
prompt immunological diagnosis and appropriate management. Aim of this
study is to detect clinical and laboratory signs of IEI, in particular
the latter by an extensive lymphocyte immunophenotyping.
Methods We retrospectively collected 47 pediatric patients with
at least one hematological disorder among which persistent/chronic ITP,
AIHA and AIN, aged 0–18 years at onset of immune cytopenias and/or
immune-dysregulation. The cohort was divided into 2 groups (IEI+ and
IEI-), based on the presence/absence of underlying IEI diagnosis. IEI+
group, formed by 19/47 individuals, included: Common variable immune
deficiency (9/19), Autoimmune lymphoproliferative syndrome (4/19),
DiGeorge syndrome (1/19) and unclassified IEI (5/19). Results
IEI prevalence among patients with ITP, AIHA, AIN and Evans Syndrome was
respectively of 42%, 64%, 36% and 62%. In IEI+ the extended
lymphocyte immunophenotyping identified the presence of statistically
significant (p-value<0.05) specific characteristics, namely
T/B lymphopenia, decrease in naїve T-cells%, switched memory B-cells%,
plasmablasts% and/or immunoglobulins, increase in effector/central
memory T-cells% and CD21low B-cells%. Conclusion A wide
focused clinical/immunophenotypical characterization of pediatric
patients with immune cytopenia can highlight specific signs of IEI,
potentially helpful in the diagnostic and clinical management,
identifying children worthy of IEI-related molecular analysis.