Serum C-reactive Protein and CRP Genotype in Pediatric Inflammatory Bowel Disease: Influence on Phenotype, Natural History, and Response to Therapy

Background:C-reactive protein (CRP) is an acute phase reactant. Patients with pediatric inflammatory bowel disease (PIBD) differ from adult patients with inflammatory bowel disease with regard to phenotype, inflammatory profile, and treatment response. We hypothesized that variations in CRP and CRP genotype influence PIBD phenotype, natural history, and remission after anti-tumor necrosis factor alpha therapy.Methods:Six single nucleotide polymorphisms tagging CRP (rs1935193, rs1130864, rs1205, rs1417938, rs11265263, and rs1800947) were genotyped in 465 patients with PIBD (diagnosed <17 yr). Phenotyping was serially performed until last follow-up and serum CRP levels recorded at diagnosis and before biological therapy in a subgroup.Results:CRP haplotype (ATGCTC) differed in those diagnosed <10 years, with rs1205T more frequent in Crohn's disease (CD) than ulcerative colitis (UC) (P = 0.009); the haplotype ATGCTC was less frequent in UC (P = 0.002). Three single nucleotide polymorphisms (rs1205, rs1130864, and rs1417938) showed association with elevated CRP levels at diagnosis. CRP genotype had no association with CD phenotype or natural history. CRP was more frequently raised at diagnosis in CD than UC (63% versus 22%, P < 0.0001). Elevated CRP at diagnosis was associated with a higher risk of progression to surgery in patients with CD (P < 0.0001) and the need for azathioprine in the overall PIBD cohort (P = 0.002). There was no effect of CRP genotype or serum CRP on the achievement of remission using anti-tumor necrosis factor alpha therapy.Conclusions:CRP and CRP genotype differ between pediatric patients with CD and UC with a high inflammatory burden at diagnosis suggesting a worse prognosis. Additional evaluation of CRP in inflammatory bowel disease pathogenesis and natural history is now warranted.