Impaired deoxyribonuclease I activity in patients with inflammatory bowel diseases.

Background and Aims. Deoxyribonuclease I (DNaseI) is an endonuclease that facilitates chromatin breakdown and promotes susceptibility to autoimmune disorders. The aim of current study was to investigate serum DNase I activity in patients with inflammatory bowel diseases (IBD). Patients and Methods. A cohort of 110 IBD patients was evaluated, aged 35 ± 12 years, 77 with Crohn's disease (CD) and 33 with ulcerative colitis (UC). 50 SLE patients and 50 healthy blood donors were examined as control groups. Results. DNase I activity in IBD patients was significantly lower than in healthy individuals, but higher than in SLE patients (P < .0001). Patients with UC showed higher DNase I activity than CD patients, P = .21. DNase I activity in female patients with IBD was significantly lower than in males, P = .024; however, no differences in DNase I activity were found in relation to gender in healthy individuals. DNase I activity has shown a strong negative correlation with the serum concentration of anti-nucleosomal antibodies in the autoimmune (SLE + IBD) cohort, as well as in the separate IBD cohort. Conclusions. Reduced serum DNase I activity probably has pathogenetic consequences in IBD. Induction of autoantibodies towards nucleosomes could be a reflection of impaired DNase I activity.

Bile acid malabsorption in inflammatory bowel disease: assessment by serum markers.

BACKGROUND: Bile acid malabsorption (BAM) is a common feature of Crohn's disease (CD). We aimed to determine whether BAM develops only in patients with a resected distal ileum or if it also occurs in patients who have not undergone surgery for CD. METHODS: The study included 347 patients with CD or ulcerative colitis (UC) and 119 healthy subjects (controls). BAM was assessed by measurement of serum levels of 7α-hydroxycholest-4-en-3-one (C4) and fibroblast growth factor 19 (FGF19). We surveyed members of the European Crohn's and Colitis Organization and International Organization for the Study of Inflammatory Bowel Disease to collect current information about BAM diagnosis. RESULTS: The severity of BAM was associated with resection of the distal ileum. Compared with controls, patients who received moderate or extensive ileal resection had significantly increased levels of serum C4 (12 versus 62 versus 243 µg/L, respectively; P < 0.001). However, BAM was also present in a substantial number of the patients with CD who were not treated by surgery who had ileitis or colitis (14% and 11%, respectively). There was an indirect, proportional relationship between levels of C4 and FGF19 (P < 0.001). CONCLUSIONS: The most severe BAM occurs in CD patients after resection of the distal ileum, but BAM can occur in surgically untreated CD patients, regardless of disease localization. Laboratory tests for BAM should become a part of the algorithm for diagnosis of CD to identify patients who might respond to therapies such as bile acid sequestrants. FGF19 appears to be a reliable marker of BAM.

Anti-inflammatory effect of biological treatment in patients with inflammatory bowel diseases: calprotectin and IL-6 changes do not correspond to sRAGE changes.

AIM: The main objective was to examine the relationship between the soluble receptor for advanced glycation end products (sRAGE) and calprotectin concentrations in faeces and serum of patients with inflammatory bowel diseases (IBD) during biological treatment with infliximab. MATERIALS AND METHODS: A total of 29 IBD patients treated with infliximab were evaluated. Calprotectin and sRAGE in serum and faeces and serum IL-6 and CRP were measured during the induction regimen of infliximab treatment at weeks (W) 0, 2 and 10. RESULTS: At W0, a significant increase in faecal calprotectin was found in IBD compared to healthy persons (690 +/- 696 microg/g and 23 +/- 7 microg/g, respectively, p < 0.001). No clear difference was found in serum sRAGE levels in IBD cohort compared to healthy controls (772 +/- 274 pg/mL and 720 +/- 107 pg/mL, respectively, p = 0.159); however, a significant negative correlation was found between faecal calprotectin levels and serum concentrations of sRAGE in the active IBD cohort (r = -0.518, p = 0.004). In the stool eluates, sRAGE levels were non-measurable. In the group of responders-to-treatment, the initial surge in both faecal and serum calprotectin levels as well as CRP and IL-6 was followed by a significant decrease on W10. Surprisingly, no significant changeovers were seen in serum sRAGE concentrations in responders neither in W2 nor in W10. CONCLUSIONS: Unlike other examined local and systemic inflammatory markers, serum sRAGE did not change during the infliximab treatment, despite the initial correlation with the degree of mucosal inflammation.

Anticarbohydrate antibodies as markers of inflammatory bowel disease in a Central European cohort.

BACKGROUND: The study discusses the role of antichitobioside carbohydrate antibody (ACCA), antilaminaribioside carbohydrate antibodies (ALCA), and antimannobioside carbohydrate antibodies (AMCA) in Central European patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Twohundred and seventy-two serum samples were used - 116 Crohn's disease (CD), 84 ulcerative colitis, and 72 healthy control samples. All samples were evaluated using enzyme-linked immunosorbent assay for the following four anticarbohydrate assays: ACCA, ALCA, AMCA, and anti-Saccharomyces cerevisiae antibodies (gASCA). RESULTS: gASCA antibodies showed the highest sensitivity (67%) for a CD diagnosis, followed by AMCA (31%), ACCA (27%), and ALCA (25%). Positivity of at least one of the four assays increased the overall sensitivity of antibody testing in CD up to 85.5%. Mean serum gASCA levels were significantly higher in CD patients who were younger at diagnosis and had a longer disease duration before blood sampling (P<0.001). In nonstricturing, nonpenetrating CD, serum gASCA levels were lower than in patients with stricturing and/or penetrating behavior (P<0.05). The strongest association of gASCA was found with ileocolonic CD and with upper gastrointestinal disease (P<0.001). No association between anticarbohydrate (AMCA, ACCA, and ALCA) antibodies and CD location, behavior, age at onset, and disease duration was found; however, that sample size of some of our subgroups was probably too small to make firm conclusions on associations with all CD phenotypes. None of the assessed anticarbohydrate assays was predictive of colonic CD in patients in whom the distinction between CD and ulcerative colitis is not obvious using routine diagnostic methods. There was no relationship between the presence or concentration of anticarbohydrate antibodies and the inflammation measured by C-reactive protein levels. CONCLUSION: The use of a panel of anticarbohydrate antibodies may provide additional help in distinguishing IBD from non-IBD disease patterns. The addition of AMCA, ALCA, and ACCA assays as IBD serology markers improves the overall sensitivity of immunological examinations in IBD; however, anticarbohydrate assays are not helpful for predicting CD behavior.

CYP7A1 promoter polymorphism -203A>C affects bile salt synthesis rate in patients after ileal resection.

Cholesterol 7alpha-hydroxylase (CYP7A1) plays a crucial role in cholesterol metabolism and has been implicated in genetic susceptibility to atherosclerosis. Thus, an understanding of its transcriptional regulation is of considerable importance. We evaluated the effect of a common -203A>C polymorphism in the CYP7A1 promoter region on the activity of CYP7A1, estimated as the ratios of serum 7alpha-hydroxycholest-4-en-3-one (C4) to either total or non-HDL-cholesterol. The study was performed on patients after resection of the distal ileum, leading to upregulation of CYP7A1 activity (n = 65). Healthy volunteers served as the control group (n = 66). Whereas higher CYP7A1 activity was associated with the -203A allele in the patient group (C4/cholesterol ratio, 29.0 vs. 14.8 microg/mmol, P = 0.032; C4/non-HDL-cholesterol ratio, 53.3 vs. 21.3 microg/mmol in -203AA and -203CC, P = 0.017, respectively), no differences were observed in the healthy controls. We conclude that under physiological conditions, the -203A>C polymorphism in the CYP7A1 gene promoter region does not seem to have any clinically relevant effect. However, in patients with severe bile salt malabsorption, this polymorphism markedly affects CYP7A1 activity.