Advances in our understanding of the molecular pathogenesis of necrotizing enterocolitis

Cai, Xue; Golubkova, Alena; Hunter, Catherine J.

doi:10.1186/s12887-022-03277-3

Cited by 6 publications

(3 citation statements)

References 62 publications

(71 reference statements)

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“…It is a multifactorial disease. 1 Neonatal sepsis is considered as a risk factor for NEC. NEC associated sepsis has high inflammatory response results in severe disease with significant immediate and late complications.…”

Section: Introductionmentioning

confidence: 99%

Necrotizing enterocolitis associated Klebsiella pneumoniae sepsis

Thomas¹

2023

Int J Contemp Pediatr

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Section: Introductionmentioning

confidence: 99%

Necrotizing enterocolitis associated Klebsiella pneumoniae sepsis

Thomas¹

2023

Int J Contemp Pediatr

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“…Several studies highlight the role of genetics in the pathogenesis of NEC. [ 26 27 28 29 ] One of the potential gene candidates that may contribute to NEC susceptibility is a single-immunoglobulin interleukin (IL)-1-related receptor (SIGIRR, NC_000011.10, Gene ID: 59307), a negative regulator of the intestinal TLR4 signaling. Mice deficient in SIGIRR demonstrate unregulated activation of the intestinal TLR4, followed by elevated intestinal inflammation and enhanced enterocyte apoptosis.…”

Section: Introductionmentioning

confidence: 99%

SIGIRR gene variants in term newborns with congenital heart defects and necrotizing enterocolitis

Zaikova,

Kaplina,

Petrova

et al. 2023

Annals of Pediatric Cardiology

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Background: Necrotizing enterocolitis (NEC) is a common gastrointestinal emergency among neonates which is characterized by acute intestinal inflammation and necrosis. The main risk factors for NEC are prematurity, low birth weight, and some preexisting health conditions such as congenital heart defects (CHDs). Investigation of the potential genetic predisposition to NEC is a promising approach that might provide new insights into its pathogenesis. One of the most important proteins that play a significant role in the pathogenesis of NEC is Toll-like receptor 4 (TLR4) which recognizes lipopolysaccharide found in Gram-negative bacteria. In intestinal epithelial cells, a protein encoded by the SIGIRR gene is a major inhibitor of TLR4 signaling. A few SIGIRR variants, including rare p.Y168X and p.S80Y, have already been identified in preterm infants with NEC, but their pathogenic significance remains unclear. This study aimed to investigate the spectrum of SIGIRR genetic variants in term newborns with CHD and to assess their potential association with NEC. Methods and Results: A total of 93 term newborns with critical CHD were enrolled in this study, 33 of them developed NEC. SIGIRR genetic variants were determined by Sanger sequencing of all exons. In total, eight SIGIRR genetic variants were identified, two of which were found only in newborns with NEC (P = 0.12). The rare missense p.S80Y (rs117739035) variant in exon 4 was found in two infants with NEC stage IIA. Two infants with NEC stage III and stage IB carried a novel duplication c. 102_121dup (rs552367848) variant in exon 10 that has not been previously associated with any clinical phenotype. Conclusions: The presence of both variants only in neonates who developed NEC, together with earlier published data, may suggest their potential contribution to the risk of developing NEC in term infants with CHD and allow planning larger cohort studies to clarify their relevance.

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“…Its recent incidences in Japan and California were reported around 1.6% and 3.9% in very low birth weight (VLBW) infants, respectively (15,16). Several reports suggested a genetic difference could explain frequency variations (17,18,19).…”

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confidence: 99%

Necrotizing enterocolitis in infants born in Japan and born to Japanese mothers in California: a retrospective cohort study

Kusuda,

Bennett,

Gould

2024

Preprint

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Objectives: There is a variation in the incidence of necrotizing enterocolitis (NEC) among countries. To investigate the influence of ethnicity, NEC incidents were compared between Japan and California. Study Design: A retrospective cohort study was conducted using neonatal databases in Japan and California, including infants between 2008 and 2019 at 22-29 gestational weeks. Infants born in Japan (JP) were compared to infants born in California to mothers born in Japan (JP-J), to mothers with Japanese ethnicity born outside Japan (JP-CA), and to non-Hispanic White mothers (NHW-CA). Results: Each cohort consisted of 52,049, 115, 226, and 12,275 infants, respectively. Unadjusted NEC incidences were significantly lower in JP (1.7% vs. 4.4% JP-J+JP-C, and 3.3% NHW-CA, respectively; p<0.01). After background adjustment, odds ratios in JP-J, JP-CA, and NHW-CA vs. JP were 3.0 (1.2-7.8), 2.9 (1.5-5.8), and 2.0 (1.6-2.5), respectively. Conclusions: The NEC incidence variation could not be explained solely based on ethnic background.

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Advances in our understanding of the molecular pathogenesis of necrotizing enterocolitis

Cited by 6 publications

References 62 publications

Necrotizing enterocolitis associated Klebsiella pneumoniae sepsis

Necrotizing enterocolitis associated Klebsiella pneumoniae sepsis

SIGIRR gene variants in term newborns with congenital heart defects and necrotizing enterocolitis

Necrotizing enterocolitis in infants born in Japan and born to Japanese mothers in California: a retrospective cohort study

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