Genetic Landscape of Non-Remitting Neutropenia in Children and Chronic Idiopathic Neutropenia in Adults

TL;DR

This study explores the genetic basis of non-remitting neutropenia in children and chronic idiopathic neutropenia in adults, finding possible links to immune dysregulation.

Contribution

The study identifies novel genetic variants and pathways potentially associated with immune dysregulation in neutropenic patients.

Findings

SPINK5, RELA, and CARD11 variants are linked to neutropenia with immune dysregulation.

Genetic differences were observed between pediatric and adult patients.

Variants are enriched in autoimmunity and immune regulation pathways.

Abstract

Non-remitting neutropenia in children and chronic idiopathic neutropenia (CIN) in adults have been described previously as peculiar subgroups of neutropenic patients carrying similar clinical and immunological features. The present collection comprising 25 subjects (16 adults and 9 children) mostly affected with mild (84%) and moderate (16%) neutropenia aimed to identify the underlying (possibly common) genetic background. The phenotype of these patients resemble the one described previously: no severe infections, presence of rheumathological signs, leukopenia in almost all patients and lymphocytopenia in one-third of the cohort. The pediatric patients did not share common genes with the adults, based on the results of the multisample test, while some singular variants in neutropenia potentially associated with immune dysregulation likely consistent with the phenotype were found. SPINK5, RELA and CARD11 were retrieved and seem to be consistent with the clinical picture characterized by neutropenia associated to immune dysregulation. The enrichment and burden tests performed in comparison with a control group underline that the products of expression by the variants involved belong to the autoimmunity and immune regulation pathways (i.e., SPINK5, PTPN22 and PSMB9). Even with the limitation of this study’s low number of patients, these results may suggest that non-remitting neutropenia and CIN in adults deserve deep genetic study and enlarged consideration in comparison with classical neutropenia.

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