Congenital Defects of the Immune System as a Manifestation of Monogenic Inflammatory Bowel Disease in Children
Year: 2024
Type: article
Study design: Observational Study
Abstract: Background. Currently, monogenic inflammatory bowel disease-like (IBD) pathologies such as congenital immunity defects, genetic epithelial barrier defects and others are becoming increasingly relevant. Objective. To analyze genetic defects associated with IBD-like immunopathology. Material and methods. The study included 46 patients with IBD manifestations aged 18 years or younger, who underwent whole-exome sequencing using the NGS method. All calculations were performed using the R statistical package, version 4.1. Results. There were identified 11 (23,9%) patients with gene mutations indicating congenital defects of the immune system (CDIS). Of these, 3 (27,3%) children were found to have abnormalities in the genes of immune dysregulation - CTLA-4 (c.151C>T (p.Arg 51*)), (FOXP3 (c.851C>T (p.Ala284Val)) and FOXP3 (c.748_750del (p.Lys250del)); 3 (27.3%) patients had abnormalities in the SLC5A1 gene (c.1666-2delA), SLC5A1 gene (c.1666-2delA and c.1680T>G(p.(Cys560Trp)) responsible for the disruption of the barrier function of the epithelium; 2 (18.2%) patients had abnormalities in the PIK3CD gene (c.3061G>A (p.Glu1021Lys)), manifested as CDIS with a predominant deficiency of antibodies; in 2 (18.2%) patients abnormalities in genes affecting cellular and humoral immunity were detected: JAK3 (c.2518C>T(p.Arg840Cys)), CD40LG (c.430G>A (p.Gly144Arg)); and in one case (9,1%) a congenital defect in the number or function of phagocytes – in CFTR gene (c.43delC (p.Leu15fs) and c.1210-11T>G) was established. According to clinical signs, patients with CDIS had only some differences from IBD patients. Conclusion. It is advisable to conduct molecular genetic analysis of target genes in IBD patients with very early onset of gastrointestinal lesions, which allows timely diagnosis of congenital defects of the immune system for subsequent prescription of adequate therapy.
Source: Hepatology and Gastroenterology
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4405653232