Ulcerative Colitis: Stange EF

Stange EF, Anonymous00187. · No affiliation provided · Z Gastroenterol. · Pubmed #11215363 No free full text.

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Wehkamp J, Koslowski M, Wang G, Stange EF. · Robert Bosch Hospital, Internal Medicine I, Stuttgart, Germany. · Mucosal Immunol. · Pubmed #19079235 No free full text.

Abstract: Defensins are endogenous antibiotics with broad microbicidal activity. A disturbed antimicrobial defense, as provided by Paneth and other epithelial defensins, seems to be a critical factor in the pathogenesis of inflammatory bowel diseases. Conspicuously, there is a relative lack of Paneth-cell alpha-defensins in ileal Crohn's disease (CD), both in the absence of a pattern recognition receptor nucleotide-binding oligomerization domain 2 (NOD2) frameshift mutation and, even more pronounced, in its presence. This deficit is independent of concurrent active inflammation and cannot be seen in active small intestinal ulcerative colitis (UC; pouchitis) as well as NOD2 wild-type graft vs. host ileitis. After intestinal transplantation, in case of NOD2 mutation, defensins are decreased before the onset of inflammation. In the majority of patients, the Paneth-cell deficiency is mediated by Wnt-TCF4, which suggests a disturbed Paneth-cell differentiation. In contrast, colonic CD is characterized by an impaired induction of mucosal beta-defensins, partly because of a low copy number of the beta-defensin gene cluster. In both ileal and colonic CD, the lack in defensins results in a broadly diminished antibacterial killing by the mucosa, which can also be found independent of inflammation. In summary, the main disease locations can be linked to distinct mechanisms of epithelial barrier dysfunction.

Gersemann M, Wehkamp J, Fellermann K, Stange EF. · Internal Medicine I, Robert Bosch Hospital, Auerbachstrasse 110, Stuttgart, Germany. · World J Gastroenterol. · Pubmed #18810765 links to  free full text

Abstract: Crohn's disease may principally involve the whole gastrointestinal tract. Most commonly, the inflammation occurs in the small intestine and/or in the colon with stable disease location over the years. The pathogenesis of both disease phenotypes is complex, the likely primary defect lies in the innate rather than adaptive immunity, particularly in the chemical antimicrobial barrier of the mucosa. Crohn's ileitis is associated with a reduced expression of the Wnt signalling pathway transcription factor T-cell factor 4 (TCF4), which is regulating Paneth cell differentiation. As a result, the alpha-defensins and principal Paneth cell products HD5 and HD6 are deficiently expressed in ileal disease, independent of current inflammation. In contrast, Crohn's colitis is typically associated with an impaired induction of the beta-defensins HBD2 and HBD3 caused by fewer gene copy numbers in the gene locus of the beta-defensins on chromosome 8. This ileal and colonic defect in innate defence mediated by a deficiency of the protective alpha- and beta-defensins may enable the luminal microbes to invade the mucosa and trigger the inflammation. A better understanding of the exact molecular mechanisms behind ileal and colonic Crohn's disease may give rise to new therapeutic strategies based on a stimulation of the protective innate immune system.

Wehkamp J, Schmid M, Stange EF. · Robert Bosch Hospital and Dr Margarete Fischer Bosch Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany. · Curr Opin Gastroenterol. · Pubmed #17545771 No free full text.

Abstract: PURPOSE OF REVIEW: Recently published studies presenting novel and relevant information on defensins and other antimicrobial peptides in Crohn's disease and ulcerative colitis are reviewed. RECENT FINDINGS: Different clinical localizations of Crohn's disease are associated with different deficiencies in epithelial and leukocyte antimicrobial peptide expression. As compared with ulcerative colitis, Crohn's disease of the colon is characterized by an impaired induction of beta defensins, and antimicrobial antiproteases elafin and SLPI, as well as the cathelicidin LL37. The attenuated induction of beta defensins is linked to fewer gene copy numbers in this locus, which is associated with colonic but not ileal Crohn's disease. In contrast, ileal Crohn's disease patients are characterized by a reduced antibacterial activity and a specific reduction of ileal Paneth cell defensins. This decrease is independent of the grade of histological inflammation and cannot be found in inflammation controls. Thus, some of these defects can be explained either by direct or indirect genetic mechanisms and appear to be primary. SUMMARY: Unlike ulcerative colitis, ileal and colonic Crohn's disease are characterized by localized deficiencies of antibacterial peptides. Understanding the precise molecular mechanisms of the defective antibacterial barrier function might provide new therapeutic directions.

Stange EF. · Abteilung für Innere Medizin 1 Schwerpunkte Gastroenterologie, Hepatologie und Endokrinologie, Robert Bosch Krankenhaus, Stuttgart, Germany. · Aliment Pharmacol Ther. · Pubmed #16961748 No free full text.

Abstract: Ulcerative colitis and, maybe to a similar extent, Crohn's disease are associated with an increased risk of colorectal carcinoma. As a consequence of this increased risk, surveillance strategies have been proposed to prevent colorectal carcinoma through early detection of dysplasia, which may herald malignant disease. These surveillance strategies are controversial for several reasons discussed in this review. It may be concluded from the relevant studies that regular use of at least 1.2 g of mesalazine per day may effectively prevent about two out of three colon cancers in ulcerative colitis. In contrast, there seems to be no role for either mercaptopurine or folic acid in protection from colon cancer.

Rothfuss KS, Stange EF, Herrlinger KR. · Robert-Bosch-Hospital, Department of Gastroenterology, Hepatology and Endocrinology, Auerbachstrasse 110, D-70376 Stuttgart, Germany. · World J Gastroenterol. · Pubmed #16937463 links to  free full text

Abstract: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that often involve organs other than those of the gastrointestinal tract. These nonintestinal affections are termed extraintestinal symptoms. Differentiating the true extraintestinal manifestations of inflammatory bowel diseases from secondary extraintestinal complications, caused by malnutrition, chronic inflammation or side effects of therapy, may be difficult. This review concentrates on frequency, clinical presentation and therapeutic implications of extraintestinal symptoms in inflammatory bowel diseases. If possible, extraintestinal manifestations are differentiated from extraintestinal complications. Special attention is given to the more recently described sites of involvement; i.e. thromboembolic events, osteoporosis, pulmonary involvement and affection of the central nervous system.

Wehkamp J, Fellermann K, Stange EF. · Department of Microbiology and Immunology, University of California, Davis, Calif., USA. · Chem Immunol Allergy. · Pubmed #15976487 No free full text.

Abstract: Crohn's disease, a transmural inflammation of the gut, has been linked to good childhood hygiene, frequent use of antibiotics before diagnosis, adherent or invasive mucosal bacteria and a break in the tolerance of luminal bacteria. A decrease or lack of mucosal peptide antibiotics may play a central role in the etiopathogenesis of Crohn's disease. The dysregulated adaptive immune system may reflect only the primary break of the mucosal defence since the immune response is mostly directed against luminal bacteria. Crohn's disease patients with ileal involvement, as compared to controls and Crohn's disease patients without ileal disease, are characterized by a diminished expression of the ileal Paneth cell defensins. This decrease is even more pronounced in Crohn's disease patients with a mutation in the NOD2 gene, which is associated with Crohn's disease and ileal involvement. NOD2 is an intracellular peptidoglycan receptor and is expressed in Paneth cells. In contrast to ulcerative colitis, Crohn's disease of the colon is characterized by an impaired induction of human beta defensins 2 and 3. The hypothesis of an impaired mucosal antibacterial activity is also consistent with the benefit from antibiotic or probiotic treatment in certain disease states.

Wehkamp J, Schmid M, Fellermann K, Stange EF. · Department of Microbiology and Immunology, University of California, Davis, CA 95616, USA. · J Leukoc Biol. · Pubmed #15618294 links to  free full text

Abstract: Crohn's disease is a chronic, inflammatory disease of the intestinal mucosa. Although intestinal bacteria are implicated in disease pathogenesis, the etiology is still unclear. The main location of disease is the small intestine (ileum) and the colon. Ileal disease has been linked to a mutation in the NOD2 gene. Defensins are antimicrobial peptides and in the ileum, are mainly expressed in Paneth cells, epithelial cells that also express NOD2. In the colon, defensins are expressed by enterocytes or metaplastic Paneth cells. Crohn's disease patients with ileal involvement, compared with controls or Crohn's patients without ileal involvement, have diminished expression of ileal Paneth cell defensins. This decrease is even more pronounced in Crohn's patients displaying a NOD2 mutation. In contrast, Crohn's disease of the colon is characterized by an impaired induction of beta-defensins in enterocytes. The colonic expression of the constitutive beta-defensin 1 is also decreased in the inflamed colonic mucosa, but this decrease is less specific to Crohn's disease, as it can also be found in ulcerative colitis patients. In conclusion, the regional localizations of Crohn's disease, ileal or colonic disease, can be linked to different defensin profiles. Crohn's disease of the ileum is associated with diminished defensin expression in Paneth cells. Crohn's disease of the colon is associated with diminished beta-defensin expression in enterocytes. Thus, it can be speculated that decreased defensin levels lead to a weakened intestinal barrier function to intestinal microbes and might be crucial in the pathophysiology of Crohn's disease.

Herrlinger K, Stange EF. · Abteilung Innere Medizin 1, Zentrum für Innere Medizin, Robert-Bosch-Krankenhaus, Stuttgart. · Dtsch Med Wochenschr. · Pubmed #15529447 No free full text.

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Hoffmann JC, Zeitz M, Bischoff SC, Brambs HJ, Bruch HP, Buhr HJ, Dignass A, Fischer I, Fleig W, Fölsch UR, Herrlinger K, Höhne W, Jantschek G, Kaltz B, Keller KM, Knebel U, Kroesen AJ, Kruis W, Matthes H, Moser G, Mundt S, Pox C, Reinshagen M, Reissmann A, Riemann J, Rogler G, Schmiegel W, Schölmerich J, Schreiber S, Schwandner O, Selbmann HK, Stange EF, Utzig M, Wittekind C. · Medizinische Klinik I mit Schwerpunkt Gastroenterologie/Infektiologie/Rheumatologie, Charité, Universitätsmedizin Berlin. · Z Gastroenterol. · Pubmed #15455267 No free full text.

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Schmid M, Fellermann K, Wehkamp J, Herrlinger K, Stange EF. · Abteilung Innere Medizin I, Robert-Bosch-Krankenhaus, Stuttgart. · Z Gastroenterol. · Pubmed #15095125 No free full text.

Abstract: Defensins are endogenous antimicrobial peptides with a broad activity spectrum. Even at micromolar concentrations gramnegative and grampositive bacteria, but also mycobacteria, as well as fungi (candida), viruses (herpes) and protozoa (giardia lamblia) are destroyed. As part of the innate immune system defensins are expressed by the intestinal epithelium and contribute to the maintenance of the mucosal barrier. This barrier appears to be defective in inflammatory bowel diseases since on one hand, the immune response is directed against the "normal" luminal bacterial flora and on the other hand, mucosal adherent and invasive bacteria have been observed in these diseases. A defective defensin expression may well explain these phenomena. Indeed, Crohn's disease of the terminal ileum, especially if associated with a NOD2 mutation, is characterised by a diminished alpha-defensin (human defensin 5 and 6) expression, and in inflamed Crohn's colitis, in contrast to ulcerative colitis, the beta-defensin (human beta-defensins 2 and 3) response is reduced. Through a deficient chemical mucosal barrier this defect could lead to increased bacterial invasion into the intestinal mucosa and might well explain an adequate inflammatory response. Although the final proof that this deficient defensin response leads to a reduced antibacterial activity of the intestinal mucosa is still lacking, the most plausible concept of pathogenesis of Crohn's disease is a defensin deficiency syndrome.

Fellermann K, Wehkamp J, Herrlinger KR, Stange EF. · Department of Internal Medicine I, Robert Bosch Krankenhaus, Stuttgart, Germany. · Eur J Gastroenterol Hepatol. · Pubmed #12840673 No free full text.

Abstract: This comprehensive review promotes the novel concept that a defensin deficiency, i.e. lack of mucosal peptide antibiotics, may play a pivotal role in the aetiopathogenesis of Crohn's disease. Such an impaired function of this chemical barrier is consistent with the epidemiological relationship of good domestic hygiene with the incidence of inflammatory bowel diseases. The disregulated adaptive immune system, formerly believed to be the major cause in the development of Crohn's disease, may reflect only the primary break of the mucosal defence since the immune response is mostly directed against lumenal bacteria. Recent work has identified five different defensins expressed in colonic mucosa. In contrast to ulcerative colitis, Crohn's disease is characterised by an impaired induction of human beta defensins 2 and 3. This deficient induction may be due to changes in the intracellular transcription by NFkappaB and the intracellular peptidoglycan receptor NOD2, mutated in Crohn's disease. These findings are consistent with the mucosal attachment of lumenal bacteria in inflammatory bowel diseases and the frequent occurrence of other infectious agents. The hypothesis of an impaired mucosal antibacterial activity is also consistent with the benefit from antibiotic or probiotic treatment in certain inflammatory bowel disease states.

Herrlinger K, Fellermann K, Stange EF. · Abteilung Innere Medizin 1, Robert-Bosch-Krankenhaus, Auerbachstrasse 110, 70376 Stuttgart. · Internist (Berl). · Pubmed #12524917 No free full text.

This publication has no abstract.

Stange EF. · Abteilung für Innere Medizin 1, Robert-Bosch-Krankenhaus Stuttgart. · Praxis (Bern 1994). · Pubmed #12501498 No free full text.

Abstract: The standard therapy in Crohn's disease and ulcerative colitis is based on corticosteroids and aminosalicylates. Chronic active as well as fulminant disease usually require immunosuppressive therapy. The new biological have mostly disappointed because of lacking efficacy (Il-10, IL-11 or others) or serious adverse events (infliximab).

Metzler J, Stange EF. · Zentrum für Innere Medizin 1, Robert-Bosch-Krankenhaus, Stuttgart. · Med Klin (Munich). · Pubmed #12078390 No free full text.

Abstract: BACKGROUND: For the treatment of inflammatory bowel diseases in recent years several antibodies, cytokines and antisense oligonucleotides have been developed using recombinant technology and were tested as so-called "biological therapeutics". EFFECTIVENESS OF BIOLOGICAL THERAPEUTICS: Infliximab, a chimeric TNF-alpha antibody, is the only biological remedy approved for the treatment of refractory and fistulizing Crohn's disease. Because of inherent risks for severe side effects, such as sepsis, the indication should be restricted to truly refractory patients and treated patients must be followed very carefully. In clinical trials other anti-TNF-alpha-effective substances (CDP 571, etanercept, thalidomide), interleukin-10, interleukin-11, ICAM-1-antisense-oligonucleotides and antibodies against alpha 4-integrin were evaluated for the treatment of Crohn's disease. In summary, for all a slight effect was noted but their place in the therapeutical repertoire is not yet defined. None of these substances is approved for patients with inflammatory bowel disease. Future developments are eagerly awaited.

Schölmerich J, Stange EF. · Klinik und Poliklinik für Innere Medizin I, Klinikum der Universität Regensburg, 93042 Regensburg. · Internist (Berl). · Pubmed #11326736 No free full text.

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Stange EF, Riemann J, von Herbay A, Lochs H, Fleig WE, Schölmerich J, Kruis W, Porschen R, Bruch HP, Zeitz M, Schreiber S, Moser G, Matthes H, Selbmann HK, Goebell H, Caspary WF. · Abteilung Innere Medizin 1 Robert-Bosch-Krankenhaus Auerbachstrasse 110 70376 Stuttgart. · Z Gastroenterol. · Pubmed #11215358 No free full text.

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Herrlinger K, Stange EF. · Medizinische Klinik I, Bereich Gastroenterologie, Universität Lübeck. · Med Klin (Munich). · Pubmed #10808301 No free full text.

Abstract: AIM: An overview on the evidence-based indications for an immunosuppressive treatment with azathioprine in chronic inflammatory bowel diseases is given. CROHN'S DISEASE: In Crohn's disease, these are the induction of remission in chronic active Crohn's disease, steroid-dependent Crohn's disease, fistulizing Crohn's disease and the maintenance of remission in Crohn's disease. The optimal dose is 2.5 mg/kg body weight, treatment should be maintained for at least 4 years. ULCERATIVE COLITIS: In ulcerative colitis, these are steroid dependency, the maintenance of remission in chronic active ulcerative colitis and the maintenance of remission after induction of remission with cyclosporin or tacrolimus in acute attacks of disease.

Ludwig D, Stange EF. · Department of Internal Medicine, University of Lübeck, Germany. · Hepatogastroenterology. · Pubmed #10690588 No free full text.

Abstract: In recent years new standards for the treatment of ulcerative colitis have evolved. This review updates evidence based therapy for the various clinical situations as well as some novel approaches. The literature search was based on Medline, Cochrane database (CD-ROM) and handsearch of relevant papers including quoted literature. There is clear-cut evidence-based support for the use of local 5-aminosalicylates in mild/moderate distal and oral 5-aminosalicylates in extensive ulcerative colitis. The administration of corticosteroids is definitely indicated in severe disease. Fulminant attacks are treated by intravenous cyclosporine or colectomy. In chronic active disease azathioprine is probably helpful. Relapse prevention again is a domain of 5-aminosalicylates or, as a novel development, E. coli Nissle. The various meta-analyses as well as the controlled trials performed in the various clinical situations typical for the manifestations of ulcerative colitis form a solid base of evidence to guide individual treatment decisions.

Fellermann K, Tanko Z, Herrlinger KR, Witthoeft T, Homann N, Bruening A, Ludwig D, Stange EF. · Department of Internal Medicine I, Robert-Bosch-Hospital, Stuttgart, Germany. · Inflamm Bowel Dis. · Pubmed #12479646 No free full text.

Abstract: Intravenous cyclosporine has proven to be an alternative to emergency colectomy in steroid-refractory ulcerative colitis, whereas the experience with FK506 is limited. In this report we compare intravenous to oral FK506 treatment in 38 patients with refractory ulcerative (n = 33) or indeterminate (n = 5) colitis. FK506 was started intravenously in the first group (n = 18) at a dose of 0.01 to 0.02 mg/kg up to 14 days, followed by 0.1 to 0.2 mg/kg orally, or was started orally at this dose in a second group (n = 20). Additional azathioprine/6-mercaptopurine was given and steroids were tapered in responding patients, followed by a dose reduction of FK506. Clinical disease activity and laboratory parameters were assessed to evaluate efficacy and safety. Primary objectives were the induction of remission (Truelove index of mild) and colectomy-free survival. Treatment lasted for a mean of 7.6 months, and the mean observation period was 16.2 months. Eighteen of 38 patients improved within 14 days, and a complete remission was achieved in 13 patients after 1 month. A colectomy within 1 month was performed in 3 of 38 patients. The overall colectomy rate was 34%. One-half of the patients with a minimum follow-up of 2 years required a colectomy. Intravenous and per oral administration were equally safe and effective. The most frequent adverse events included tremor, hyperglycemia, hypertension, and infection, but none were severe. Renal impairment was rare and subsided upon drug withdrawal. In conclusion. FK506 is effective in the treatment of refractory colitis with per oral dosing being equivalent to intravenous administration.

Fellermann K, Steffen M, Stein J, Raedler A, Hämling J, Ludwig D, Loeschke K, Stange EF. · Department of Internal Medicine I, Division of Gastroenterology, University of Lübeck, Lübeck, Germany. · Aliment Pharmacol Ther. · Pubmed #10651657 links to  free full text

Abstract: BACKGROUND: Mycophenolate mofetil (MMF) is a new immunosuppressant with pharmacodynamic properties comparable to azathioprine. Recent reports found MMF to be effective in inflammatory bowel disease (IBD). METHODS: An open-label prospective and uncontrolled multicentre 6 month trial of MMF in combination with steroids was conducted in 24 chronic active IBD patients. A daily steroid demand of >/= 10 mg prednisone in the preceding 2 months and a Crohn's disease activity index (CDAI) > 150, or moderate to severe activity according to Truelove, served as criteria for chronic activity. The treatment consisted of a steroid pulse and tapering protocol in combination with MMF 2 g/day. A prednisone dose of 5 mg/day was maintained during months 4-6. The primary end-point was induction and maintenance of remission. RESULTS: Only 10 of 24 patients had achieved remission after 3 months. All but one Crohn's disease patient had relapsed by the end of the study at 6 months. Depression and migraine necessitated drug withdrawal in two patients. CONCLUSION: In conclusion, MMF 2 g/day was unable to induce and maintain remission for a period of 6 months in 23 of 24 chronic active IBD patients. Further controlled investigations are required in view of recent conflicting reports.

Gersemann M, Becker S, Kübler I, Koslowski M, Wang G, Herrlinger KR, Griger J, Fritz P, Fellermann K, Schwab M, Wehkamp J, Stange EF. · Department of Internal Medicine I, Robert Bosch Hospital, Stuttgart, Germany. · Differentiation. · Pubmed #19281767 No free full text.

Abstract: Goblet cells are mucin-secreting intestinal cells forming the mucus layer that protects the mucosal surface. Ulcerative colitis (UC) has been associated with a defective colonic mucus layer and a reduced number of goblet cells. In experimental animals, colonic goblet cell differentiation is regulated by interacting transcription factors Hath1, KLF4 and the Notch, as well as Wnt pathways, whereas data in humans are limited. We investigated goblet cell differentiation factors and mucins in controls and in inflammatory bowel diseases (IBDs). We performed real-time PCR for Hath1, KLF4, several ligands, receptors and target genes of the Notch and Wnt pathways, as well as several mucins in biopsies from the sigmoid colon of controls (n=21), Crohn's disease (CD, n=48) and UC (n=40). In addition, Hath1 protein was quantitated with Western blot and localized with immunohistochemistry. Notably, the degree of inflammation as measured by IL-8 and histology was similar in both disease entities. The proportion of goblet cells was lowered in both IBDs, but specifically diminished in the upper third of the crypt in UC. Comparable levels of inflammation induced both Hath1 (2.0-fold, p<0.001) and KLF4 (1.8-fold for KLF4, p=0.031) mRNA expression in CD but not in UC (0.8-0.9-fold, ns). The differential induction was confirmed for Hath1 protein using Western blot. Hath1 immunostaining was found mostly in the lower half of the colonic crypts. Hath1, KLF4 and the Notch target gene Hes1 were significantly (p<0.001) and positively correlated. Moreover, both Hath1 and KLF4 were correlated (p<0.001) with MUC1, MUC2 as well as MUC4 in all control and IBD cohorts. The results indicate that both transcription factors are key regulators of goblet cell differentiation and mucin formation in the human colon. Conspicuously, inflammation is associated with an enhanced goblet cell differentiation in CD but not in UC, a defect possibly of pathogenic importance.

Koslowski MJ, Kübler I, Chamaillard M, Schaeffeler E, Reinisch W, Wang G, Beisner J, Teml A, Peyrin-Biroulet L, Winter S, Herrlinger KR, Rutgeerts P, Vermeire S, Cooney R, Fellermann K, Jewell D, Bevins CL, Schwab M, Stange EF, Wehkamp J. · Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Stuttgart, Germany. · PLoS One. · Pubmed #19221600 links to  free full text

Abstract: Reduced expression of Paneth cell antimicrobial alpha-defensins, human defensin (HD)-5 and -6, characterizes Crohn's disease (CD) of the ileum. TCF-4 (also named TCF7L2), a Wnt signalling pathway transcription factor, orchestrates Paneth cell differentiation, directly regulates the expression of HD-5 and -6, and was previously associated with the decrease of these antimicrobial peptides in a subset of ileal CD. To investigate a potential genetic association of TCF-4 with ileal CD, we sequenced 2.1 kb of the 5' flanking region of TCF-4 in a small group of ileal CD patients and controls (n = 10 each). We identified eight single nucleotide polymorphisms (SNPs), of which three (rs3814570, rs10885394, rs10885395) were in linkage disequilibrium and found more frequently in patients; one (rs3814570) was thereby located in a predicted regulatory region. We carried out high-throughput analysis of this SNP in three cohorts of inflammatory bowel disease (IBD) patients and controls. Overall 1399 healthy individuals, 785 ulcerative colitis (UC) patients, 225 CD patients with colonic disease only and 784 CD patients with ileal involvement were used to determine frequency distributions. We found an association of rs3814570 with ileal CD but neither with colonic CD or UC, in a combined analysis (allele positivity: OR 1.27, 95% CI 1.07 to 1.52, p = 0.00737), which was the strongest in ileal CD patients with stricturing behaviour (allele frequency: OR 1.32, 95% CI 1.08 to1.62, p = 0.00686) or an additional involvement of the upper GIT (allele frequency: OR 1.38, 95% CI 1.03 to1.84, p = 0.02882). The newly identified genetic association of TCF-4 with ileal CD provides evidence that the decrease in Paneth cell alpha-defensins is a primary factor in disease pathogenesis.

Stange EF, Travis SP. · Robert Bosch Krankenhaus, Stuttgart, Germany. · Gut. · Pubmed #18448568 No free full text.

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Herrlinger K, Stange EF. · Zentrum für Innere Medizin I, Robert-Bosch-Krankenhaus, Auerbachstrasse 110, Stuttgart. · Med Klin (Munich). · Pubmed #18270665 No free full text.

This publication has no abstract.