Primary Immunodeficiency in Children With Autoimmune Cytopenias: Retrospective 154-Patient Cohort

Abstract

BackgroundPrimary immunodeficiency is common among patients with autoimmune cytopenia.ObjectiveThe purpose of this study is to retrospectively identify key clinical features and biomarkers of primary immunodeficiency (PID) in pediatric patients with autoimmune cytopenias (AIC) so as to facilitate early diagnosis and targeted therapy.MethodsElectronic medical records at a pediatric tertiary care center were reviewed. We selected 154 patients with both AIC and PID (n=17), or AIC alone (n=137) for inclusion in two cohorts. Immunoglobulin levels, vaccine titers, lymphocyte subsets (T, B and NK cells), autoantibodies, clinical characteristics, and response to treatment were recorded.ResultsClinical features associated with AIC-PID included splenomegaly, short stature, and recurrent or chronic infections. PID patients were more likely to have autoimmune hemolytic anemia (AIHA) or Evans syndrome than AIC-only patients. The AIC-PID group was also distinguished by low T cells (CD3 and CD8), low immunoglobulins (IgG and IgA), and higher prevalence of autoantibodies to red blood cells, platelets or neutrophils. AIC diagnosis preceded PID diagnosis by 3 years on average, except among those with partial DiGeorge syndrome. AIC-PID patients were more likely to fail first-line treatment.ConclusionsAIC patients, especially those with Evans syndrome or AIHA, should be evaluated for PID. Lymphocyte subsets and immune globulins serve as a rapid screen for underlying PID. Early detection of patients with comorbid PID and AIC may improve treatment outcomes. Prospective studies are needed to confirm the diagnostic clues identified and to guide targeted therapy.

Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study

“…This study confirms the strong relationship between AICs and IEI (13,16), focusing on the potential role of extensive multiparametric flow cytometry and PCA as screening tools for an underlying genetic disorder. T cell phenotypes analyzed before 2 nd -or 3 rdline treatment revealed an imbalanced T CD4+ and CD8+ profile in patients with AIC-sIEI.…”

“…In a clinical context, this corresponds to autoimmune features with or without lymphoproliferation, which are typically associated with PIRDs (57). The heterogeneity of lymphocyte frequency data is in line with the high variability of IEIs that may clinically display autoimmune cytopenias (8,13). These include CVID, which typically bears abnormal B cell subsets including a reduction in switched memory B cells (CD19+CD27+IgD-) frequency (58), especially in patients with autoimmune features (59).…”

“…Patients presenting with chronic/refractory AIC require a differential clinical management than patients with acute, transient AIC, which may need to be further adapted in presence of additional signs of immune dysregulation ( 13 ). In particular, in our cohort a higher proportion of AIC-sIEI patients underwent 2 nd - and 3 rd -line treatment, and for 6 patients the severity of their clinical status led to the choice of HSCT as definitive therapy.…”

“…Moreover, the combination of AIHA and immune thrombocytopenia (ITP) is often the clinical presentation of a PIRD (9)(10)(11), and potentially bears a genetic explanation in 65% of cases (12). Indeed, some specific immunological alterations, if accompanied with AIHA, ITP, autoimmune neutropenia (AIN), or their combinations (Evans syndrome, ES) could be significant red flags for an associated IEI (13). These include both humoral and cell-mediated immune defects, like reduced serum immunoglobulin levels and low T cell counts (3,12,14,15), while only scant evidence regarding deeper immunological studies in AICs is available (16).…”

Endocrinopathies in Inborn Errors of Immunity

“…However, other causes affect linear growth, e.g., undernutrition, rheumatologic inflammation, chronic renal failure, malignancy, respiratory failure, severe cardiac diseases, and genetic disease with primary effects on growth. Indeed, despite the risk of growth failure in IEI ( 69 ), GH deficiency or hypothyroidism is not documented in most IEI patients with growth failure ( 70 ). This suggests that the causes of growth failure in patients with IEI are heterogeneous.…”