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Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX3CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX3CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses. [ABSTRACT FROM AUTHOR]

Background and aim The incidence of Crohn's disease (CD) is continuing to rise in several countries and in others it appears to have already levelled off after a period of increase. We updated our previous population-based study, by re-extraction of all information on patients diagnosed with CD between 1963 and 2010. Our aim was to assess temporal trends in incidence, prevalence and disease phenotype at diagnosis. Methods Patients of all ages with a potential diagnosis of CD were identified retrospectively by evaluation of medical notes of all current and previous patients at the colitis clinic, Örebro University Hospital amended by computerised search in the inpatient, outpatient, primary care and histopathological records. Diagnosis was confirmed by subsequent evaluation of medical notes. Disease phenotype was defined according to the Montreal classification. Results The incidence increased over time, especially among Crohn's disease, A1 and A3. SaTScan model revealed a statistically significant high incidence during 1991–2010 (p = 0.0001). The median age at diagnosis increased from 28 (3–79) years to 37 (5–87) years (p = 0.0002). The point prevalence increased from 21/10 5 (14–32) in 1965 to 267/10 5 (244–291) in 2010. Non-stricturing and non-penetrating disease at diagnosis increased from 12.5% in 1963–1965 to 82.3% in 2006–2010 (p < 0.0001). Conclusion The incidence of CD increased over time, although it seemed to be plateauing during the most recent decades. A striking increase in non-stricturing, non-penetrating disease at diagnosis was observed, suggesting earlier diagnosis or phenotypic change. The observed point prevalence in 2010 is among the highest reported. [ABSTRACT FROM AUTHOR]

Collagenous colitis and lymphocytic colitis, together constituting microscopic colitis, are common causes of chronic diarrhea. They are characterized clinically by chronic nonbloody diarrhea and a macroscopically normal colonic mucosa where characteristic histopathological findings are seen. Previously considered rare, they now have emerged as common disorders that need to be considered in the investigation of the patient with chronic diarrhea. The annual incidence of each disorder is five to ten per 100,000 inhabitants, with a peak incidence in 60- to 70-year-old individuals and a predominance of female patients in collagenous colitis. The etiology and pathophysiology are not well understood, and the current view suggests an uncontrolled mucosal immune reaction to various luminal agents in predisposed individuals. Clinical symptoms comprise chronic diarrhea, abdominal pain, fatigue, weight loss, and fecal incontinence that may impair the patient's health-related quality of life. An association is reported with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. The best-documented treatment, both short-term and long-term, is budesonide, which induces clinical remission in up to 80% of patients after 8 weeks' treatment. However, after successful budesonide therapy is ended, recurrence of clinical symptoms is common, and the best possible long-term management deserves further study. The long-term prognosis is good, and the risk of complications, including colonic cancer, is low. We present an update of the epidemiology, pathogenesis, diagnosis, and management of microscopic colitis. [ABSTRACT FROM AUTHOR]

Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established an in vitro model to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4+ T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-γ, IL-17A, IL-6, and IL-1β and the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4+ T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, our in vitro model reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro- and anti-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Abstract: Background: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory bowel disorders of unknown etiology. This study investigated phenotypic characteristics of the mucosal lymphocytes in CC and LC. Methods: Lamina propria and intraepithelial lymphocytes (LPLs, IELs) isolated from mucosal biopsies from CC (n=7), LC (n=6), as well as LC or CC patients in histopathological remission, (LC-HR) (n=6) and CC-HR (n=4) and non-inflamed controls (n=10) were phenotypically characterized by four-color flow cytometry. Results: The proportions of CD8+ IELs were increased in CC and LC (p<0.01) compared to controls. Increased proportions of CD45RO+CD8+ IELs and LPLs were observed in LC and even more in CC patients (p<0.01). Both CC (p<0.05) and LC patients had elevated proportions of CD4+8+ IELs and LPLs compared to controls. The proportions of CD45RO+ cells were increased in CD4+8+ IELs and LPLs (p<0.05) in CC and LC patients compared to controls. Both CC (p<0.05) and LC patients had higher proportions of Ki67+CD8+ IELs and LPLs compared to controls. In contrast, decreased proportions of CD4+ LPLs were observed in CC and LC as well as CD4+ IELs in LC compared to controls. Increased proportions of Ki67+CD4+ IELs and LPLs (p<0.05) were observed in CC and LC patients. CC-HR but not LC-HR patients demonstrated normalized proportions of both IELs and LPLs compared to CC and LC patients respectively. Conclusion: LC and CC patients have differences in mucosal lymphocyte subsets, with increased proportions of Ki67+ and CD45RO+ CD8+ and CD4+8+ mucosal T cells. [Copyright &y& Elsevier]

The changing epidemiology of inflammatory bowel disease (IBD) across time and geography suggests that environmental factors play a major role in modifying disease expression. Disease emergence in developing nations suggests that epidemiological evolution is related to westernisation of lifestyle and industrialisation. The strongest environmental associations identified are cigarette smoking and appendectomy, although neither alone explains the variation in incidence of IBD worldwide. Urbanisation of societies, associated with changes in diet, antibiotic use, hygiene status, microbial exposures and pollution have been implicated as potential environmental risk factors for IBD. Changes in socioeconomic status might occur differently in different geographical areas and populations and, consequently, it is important to consider the heterogeneity of risk factors applicable to the individual patient. Environmental risk factors of individual, familial, community-based, countrybased and regionally based origin may all contribute to the pathogenesis of IBD. The geographical variation of IBD provides clues for researchers to investigate possible environmental aetiological factors. The present review aims to provide an update of the literature exploring geographical variability in IBD and to explore the environmental risk factors that may account for this variability. [ABSTRACT FROM AUTHOR]

Celiac disease ( CeD) is a disease more prevalent and multisymptomatic than was earlier recognized. Whereas prompt initiation of gluten-free diet ( GFD) is beneficial in relieving the symptoms, an accurate CeD diagnosis is necessary also to avoid years of restricted diet on uncertain grounds. We propose a new diagnostic method, based on elution of deposited antibodies against transglutaminase (anti-t TG) from duodenal biopsies in patients with symptoms and screening serology analyses suggestive of CeD. The eluates were analyzed in a Phadia 250 fluoroimmunoassay, demonstrating elevated concentrations of anti-t TG in CeD patients, corresponding to serology and histopathology findings. In one case histology was inconclusive, displaying only unspecific inflammation, but eluted anti-t TG was positive. This patient has clinically improved following GFD. We conclude that our novel method represents a new tool in the diagnostic work up in CeD. The detection of deposited anti-t TG at the site of inflammation appears to provide a high sensitivity and specificity using a technique that is quick, simple and reliable. Further studies are needed for optimization and elucidation of suitable applications for this elution method. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients’ health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis. Methods: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n =8931). Results: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p <0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being. Conclusion: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ∼20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Crohn's disease (CD) is characterized by overproduction of proinflammatory cytokines like interleukin (IL)-1β. Production of mature IL-1β is dependent on a caspase-1-activatingprotein complex called the NALP3 inflammasome, composed of NALP3, ASC, and CARD8. NALP3 shares structural similarities with Nod2, and both of these proteins are required forbacteria-induced IL-1β secretion. The combination of the polymorphisms CARD8 (C10X)and NALP3 (Q705K) was recently shown to be associated with rheumatoid arthritis.Our aim was to investigate whether these combined polymorphisms play a role in the susceptibility to CD.METHODS:The study included 498 CD patients in two cohorts from different regions and 742 control individuals from a Swedish population. DNA was isolated from whole blood. Polymorphisms of (Q705K) NALP3 and (C10X) CARD8, as well as the Nod2 variants, R702W and G908R, were genotyped using the Taqman single nucleotide polymorphism assay. The Nod2 frameshift mutation, L1007fs, was detected by Megabace SNuPe genotyping.RESULTS:Our results show that men who have both the C10X and Q705K alleles in CARD8 and NALP3, and who express wild-type alleles of Nod2 are at an increased risk of developing CD (odds ratio, OR: 3.40 range: 1.32–8.76); P=0.011). No association with these polymorphisms was found in women (OR: 0.89 (range: 0.44–1.77); P=0.74).CONCLUSIONS:We suggest a role for combined polymorphisms in CARD8 and NALP3 in the development of CD in men, with obvious sex differences in the genetic susceptibility pattern. These findings give further support to the importance of innate immune responses in CD.Am J Gastroenterol 2009; 104:1180–1188; doi:10.1038/ajg.2009.29; published online 24 March 2009 [ABSTRACT FROM AUTHOR]