Protein Network Alterations in G-CSF Treated Severe Congenital Neutropenia Patients and Beneficial Effects of Oral Health Intervention

Proteomics Clin Appl. 2024 Nov;18(6):e202400064. doi: 10.1002/prca.202400064. Epub 2024 Aug 3.

Abstract

Purpose: Severe congenital neutropenia (SCN) is a raredisorder characterized by diminished neutrophil levels. Despite granulocytecolony-stimulating factor (G-CSF) treatment, SCN patients remain still prone tosevere infections, including periodontal disease-a significant oral healthrisk. This study investigates the host proteome and metaproteome in saliva andgingival crevicular fluid (GCF) of G-CSF-treated patients.

Experimental design: We used label-free quantitative proteomics on saliva and GCF samples from SCN patients before (n = 10, mean age: 10.7 ± 6.6 years) and after a 6-month oral hygiene intervention (n = 9,mean age: 11.6 ± 5.27 years), and from 12 healthy controls.

Results: We quantified 894 proteins in saliva (648 human,246 bacterial) and 756 proteins in GCF (493 human, 263 bacterial). Predominant bacterial genera included Streptococcus, Veillonella, Selenomonas, Corynebacterium, Porphyromonas, and Prevotella. SCN patients showed reduced antimicrobial peptides (AMPs) and elevated complement proteins compared tohealthy controls. Oral hygiene intervention improved oral epithelial conditionsand reduced both AMPs and complement proteins.

Conclusions and clinical relevance: SCN patients have aunique proteomic profile with reduced AMPs and increased complement proteins, contributing to infection susceptibility. Oral hygiene intervention not onlyimproved oral health in SCN patients but also offers potential overall therapeuticbenefits.

Keywords: antimicrobial peptides; complement proteins; gingival crevicular fluid; saliva; severe congenital neutropenia.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Congenital Bone Marrow Failure Syndromes* / drug therapy
  • Congenital Bone Marrow Failure Syndromes* / metabolism
  • Female
  • Gingival Crevicular Fluid / metabolism
  • Granulocyte Colony-Stimulating Factor* / metabolism
  • Humans
  • Male
  • Neutropenia* / congenital
  • Neutropenia* / drug therapy
  • Neutropenia* / metabolism
  • Neutropenia* / microbiology
  • Oral Health*
  • Oral Hygiene
  • Proteomics
  • Saliva / metabolism
  • Saliva / microbiology

Substances

  • Granulocyte Colony-Stimulating Factor

Supplementary concepts

  • Neutropenia, Severe Congenital, Autosomal Recessive 3