Review article: exposure to microbes and risk of coeliac disease

Størdal, Ketil; Kahrs, Christian; Tapia, German; Agardh, Daniel; Kurppa, Kalle; Stene, Lars C.

doi:10.1111/apt.16161

Cited by 24 publications

(10 citation statements)

References 183 publications

(189 reference statements)

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“…We rely on a correct interpretation of signs of infections by caregivers, and subclinical infections will not be captured. However, these are less likely to induce interferon response and other immune reactions that are likely involved in any association between infections and CD/T1D 1 . It remains a limitation of our study that biomarkers were not collected to characterize whether non‐symptomatic infections, including enteroviruses, 4 parechovirus, 36 and reoviruses, 37 could be associated with genetic susceptibility variants for CD and T1D.…”

Section: Discussionmentioning

confidence: 99%

“…However, these are less likely to induce interferon response and other immune reactions that are likely involved in any association between infections and CD/T1D. 1 It remains a limitation of our study that biomarkers were not collected to characterize whether non-symptomatic infections, including enteroviruses, 4 parechovirus, 36 and reoviruses, 37 could be associated with genetic susceptibility variants for CD and T1D. Further, the SNPs that are included in the non-HLA GRS could have protective or predisposing effects.…”

Section: Discussionmentioning

confidence: 99%

“…Genes are fundamental in the etiology of common autoimmune diseases including type 1 diabetes (T1D) and celiac disease (CD). Environmental factors for T1D and CD are less established, but several lines of evidence point toward microbial factors 1,2 . Cohort studies suggest that infections are more common in early life for those who later develop CD 1 .…”

Section: Introductionmentioning

confidence: 99%

“…Environmental factors for T1D and CD are less established, but several lines of evidence point toward microbial factors 1,2 . Cohort studies suggest that infections are more common in early life for those who later develop CD 1 . Enterovirus infections have been associated with the risk of subsequent T1D autoimmunity and clinical disease 3 and recently also CD 4–6 …”

Section: Introductionmentioning

confidence: 99%

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Genotypes predisposing for celiac disease and autoimmune diabetes and risk of infections in early childhood

Størdal,

Tapia,

Lund‐Blix

et al. 2023

J. pediatr. gastroenterol. nutr.

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ObjectivesInfections in early childhood have been associated with risk of celiac disease (CD) and type 1 diabetes (T1D). We investigated whether this is driven by susceptibility genes for autoimmune disease by comparing infection frequency by genetic susceptibility variants for CD or T1D.MethodsWe genotyped 373 controls and 384 children who developed CD or T1D in the population‐based Norwegian Mother, Father and Child Cohort study (MoBa) study for human leukocyte antigen (HLA)‐DQ, FUT2, SH2B3, and PTPN22, and calculated a weighted non‐HLA genetic risk score (GRS) for CD and T1D based on over 40 SNPs. Parents reported infections in questionnaires when children were 6 and 18 months old. We used negative binomial regression to estimate incidence rate ratio (IRR) for infections by genotype.ResultsHLA genotypes for CD and T1D or non‐HLA GRS for T1D were not associated with infections. The non‐HLA GRS for CD was associated with a nonsignificantly lower frequency of infections (aIRR: 0.95, 95% CI: 0.87−1.03 per weighted allele score), and significantly so when restricting to healthy controls (aIRR: 0.89, 0.81−0.99). Participants homozygous for rs601338(A;A) at FUT2, often referred to as nonsecretors, had a nonsignificantly lower risk of infections (aIRR: 0.91, 95% CI: 0.83−1.01). SH2B3 and PTPN22 genotypes were not associated with infections. The association between infections and risk of CD (OR: 1.15 per five infections) was strengthened after adjustment for HLA genotype and non‐HLA GRS (OR: 1.24).ConclusionsHLA variants and non‐HLA GRS conferring susceptibility for CD were not associated with increased risk of infections in early childhood and is unlikely to drive the observed association between infections and risk of CD or T1D in many studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genotypes predisposing for celiac disease and autoimmune diabetes and risk of infections in early childhood

Størdal,

Tapia,

Lund‐Blix

et al. 2023

J. pediatr. gastroenterol. nutr.

Self Cite

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“…Although the timing and nature of such environmental factors are largely unknown, 55 , 58 multiple studies have acknowledged the implication of infections in disease pathogenesis. 59 – 64 Conversely, CeD patients may also be susceptible to infectious diseases. 65 – 68 …”

Section: Celiac Diseasementioning

confidence: 99%

Coronavirus disease 2019 and gastrointestinal disorders in children

Tjernberg

Malmborg

Mårild

2023

Therap Adv Gastroenterol

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During the past 3 years, the coronavirus disease 2019 (COVID-19) pandemic has had a great impact on people all over the world. However, it has become evident that disease manifestations and severity differ across age groups. Most children have a milder disease course than adults but possibly more pronounced gastrointestinal (GI) symptoms. Given the child’s developing immune system, the impact of COVID-19 on disease development may differ compared to adults. This study reviews the potential bi-directional relationship between COVID-19 and GI diseases in children, focusing on common pediatric conditions such as functional GI disorders (FGID), celiac disease (CeD), and inflammatory bowel disease (IBD). Children with GI diseases, in general, and CeD and IBD, in particular, do not seem to have an increased risk of severe COVID-19, including risks of hospitalization, critical care need, and death. While infections are considered candidate environmental factors in both CeD and IBD pathogenesis, and specific infectious agents are known triggers for FGID, there is still not sufficient evidence to implicate COVID-19 in the development of either of these diseases. However, given the scarcity of data and the possible latency period between environmental triggers and disease development, future investigations in this field are warranted.

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Transglutaminase 2 affinity and enzyme‐substrate intermediate stability as determining factors for T‐cell responses to gluten peptides in celiac disease

et al. 2022

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The adaptive immune response of celiac disease (CeD) involves presentation of gluten peptides to CD4 + T cells by transglutaminase 2 (TG2) specific B cells. This B-cell/T-cell crosstalk is facilitated by involvement of TG2:gluten peptide complexes that act principally in the form of enzyme-substrate intermediates. Here, we have addressed how gluten peptide affinity and complex stability in the presence of secondary substrates affect the uptake of TG2:gluten peptide complexes by TG2-specific B cells and the activation of gluten-specific T cells. We studied affinity of various gluten peptides for TG2 by biochemical assay, and monitored uptake of gluten peptides by TG2-specific B cells by flow cytometry. Crosstalk between TG2-specific B cells and gluten-specific T cells was assayed with transfectants expressing antigen receptors derived from CeD patients. We found that gluten peptides with high TG2 affinity showed better uptake by TG2specific B cells. Uptake by B cells, and subsequent activation of T cells, was negatively affected by polyamines acting as secondary TG2 substrates. These results show that affinity between gluten peptide and TG2 governs the selection of T-cell epitopes via enhanced uptake of TG2:gluten complexes by TG2-specific B cells, and that exogenous polyamines can influence the CeD immune responses by disrupting TG2:gluten complexes.

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Review article: exposure to microbes and risk of coeliac disease

Cited by 24 publications

References 183 publications

Genotypes predisposing for celiac disease and autoimmune diabetes and risk of infections in early childhood

Genotypes predisposing for celiac disease and autoimmune diabetes and risk of infections in early childhood

Coronavirus disease 2019 and gastrointestinal disorders in children

Transglutaminase 2 affinity and enzyme‐substrate intermediate stability as determining factors for T‐cell responses to gluten peptides in celiac disease

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