Biochemical Markers, Genotype, and Inflammation in Pediatric Inflammatory Bowel Disease: A Danish Population-Based Study

Abstract

Background: Our aim was to characterize the biochemical markers at diagnosis in patients with inflammatory bowel disease (IBD), to assess the utility of these to predict disease course and investigate if genotype influences biochemical markers of inflammation. Summary: Patients were included from a population-based pediatric IBD cohort from Eastern Denmark. Data on biochemical markers and medical as well as surgical treatment were registered at diagnosis, 30 days, 6 and 12 months after diagnosis. Fifty-two single nucleotide polymorphisms (SNPs) known to be associated with IBD were selected for genotyping based on previous genetic studies. Key messages: A total of 190 IBD patients (97 ulcerative colitis [UC], 87 Crohn’s disease [CD], and 6 IBD unclassified) were included. UC patients with extensive disease had higher C-reactive protein, erythrocyte sedimentation rate, and platelet count at diagnosis compared to UC patients with less extensive disease. No similar differences between disease extent groups were found in CD. Low albumin at diagnosis was associated with an increased risk of surgery in both UC (OR 1.35; 95% CI: 1.05–1.75) and CD patients (OR 1.23; 95% CI: 1.01–1.48) and increased use of azathioprine and anti-tumor necrosis factor alpha use in the total IBD cohort (OR 1.15; 95% CI: 1.04–1.27 and OR 1.19 [1.08–1.34]). One SNP (rs4986791 in the TLR-4 locus) and 2 SNPs (rs6785049 in the Pregnane-x-receptor gene and rs10500264 in the SLCA10 gene) were associated with a change in albumin and hemoglobin over time respectively in our IBD cohort. Our study confirms albumin to be a marker of severe disease course. Furthermore, the patient’s genotype possibly affects the inflammatory response. Future studies in larger pediatric cohorts are needed to confirm our findings.

Diagnostic utility and phenotype correlation of serum ASCA and ANCA in pediatric inflammatory bowel disease

“…Based on our results, serum IgG and IgA titers may be useful as disease activity markers in the evaluation of pediatric IBD. Besides, our study found a strong correlation between serum albumin levels and quantitative values of IgG and IgA ASCAs, which may indicate that greater quantitative levels re ect more severe illness, similar to earlier studies demonstrating that serum albumin might indicate disease severity [19].…”

Long-term outcome of immunomodulator use in pediatric patients with inflammatory bowel disease

“…Crohn's patients with higher CRP and lower albumin at diagnosis are expected to have a more aggressive course [12,[47][48][49]. Also, growth failure has fairly consistently been associated with disease severity at diagnosis [50,51].…”

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease

“…This may indicate that greater quantitative levels of serum ASCA titers reflect more severe disease, similar to earlier studies demonstrating that serum albumin might indicate disease severity. 19 In the correlation analysis, when the log value was applied to ASCA IgG and IgA titer and variables, the effect size of CRP and ESR was found to be larger, showing that serum ASCA IgG and IgA titer are more related to inflammatory responses than other variables. Based on our results, serum ASCA IgG and IgA titers may be useful as serological biomarkers in evaluating the disease activity of pediatric IBD.…”