Neutropenia as a marker of primary immunodeficiency

Abstract

Introduction. Neutropenia is a heterogeneous group of disorders with different etiological factors, including inborn errors of immunity. Congenital neutropenia may present as isolated neutropenia or as part of broader syndromic disorders. Management strategies include wide spectrum of approaches such as infection prophylaxis, granulocyte colony-stimulating factor (G-CSF) therapy, hematopoietic stem cell transplantation and others. Understanding the molecular mechanisms underlying genetic neutropenia not only enhances diagnostic precision but also opens avenues for targeted therapies. Materials/Methods. Ukrainian Registry for primary immunodeficiencies was reviewed in order to identify the patients with neutropenia and to analyze the genetic spectrum of neutropenia and the impact of genetic testing on treatment choices. Results. 118 patients with neutropenia were identified, in 63/118 (53.4%) neutropenia was an isolated manifestation, in others it was combined with other cytopenias, T- or B-cell immunodeficiency or syndromic features. 67 out of 118 (56.7%) of patients have genetical confirmation: ELANE - 9, HAX1 – 3, SBDS - 5, SRP54 – 1, FAS – 5, CD40L – 2, PIK3CD – 3 and 1 PIK3CD+TACI, TACI - 8, NFKB1 – 1, G6PТ1 – 2, TINF2 – 1, TERT – 1, DCK1+TCN2 – 1, RTEL1 – 5, ERCC6L2 – 2, FANCA -1, FANCD2 – 1, DADA2 – 2, GATA2 – 4, AK-2 – 1, CXCR4 – 5, ARPC1B – 1, VPS13B – 1, KMT2D - 1. In the majority of cases (55 out of 67, 82%) the genetic diagnosis was crucial for the choice of treatment management, moving into the decision of HSCT in 22 patients, rapamycin in patients with ALPS (FAS) and APDS, monitoring and IG substitution therapy for associated antibody deficiency, metabolic drugs in glycogenosis due to G6PТ1 defect. Conclusion. In the majority of genetically confirmed cases of neutropenia was a part of a syndromic diagnosis. Awareness of neutropenia as possible feature of PID and genetic testing opens up opportunities for diagnosis, which may be crucial in the choice of therapy. Advances in genetic testing, especially next-generation sequencing, have improved diagnostic accuracy and enabled early intervention.