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Background: The expression of CD70 on T cells is greatly enhanced by antigen-presenting cell (APC)-associated signals, such as tumour necrosis factor(TNF)-α, which is constitutionally high in patients with inflammatory bowel disease (IBD). Experimentally, the chronic activation of CD27 as a result of the constitutive expression of CD70 leads to the demise of B cells in bone marrow (BM) and the secondary lymphoid organs. The aim of this study was to assess the number and phenotype of circulating B cell in untreated IBD patients and their counterparts treated with biological anti-TNF drugs., Methods: The study involved 13 untreated IBD patients, 36 IBD patients treated with biological drugs, and 10 healthy controls. The B cell phenotypes were assessed by means of flow cytometry using monoclonal antibodies specific for CD20, CD19, CD3, CD27 and CD43. In order to evaluate B cell development in bone marrow and peripheral B cell activation, we identified four B cell subsets: hematogones (HBs: CD20 + 19 + 3 - 27 - 43 + ), memory B cells (MBs: CD20 + 19 + 3 - 27 + 43 - ), pre-plasmablasts (PPBs: CD20 + 19 + 3 - 27 + 43 + ), and plasmablasts (PBs: CD20 - 19 + 3 - 27 + 43 + )., Results: The total number of B cells in the untreated patients was three times lower than that in the patients treated with biological drug (p<0.001), and half that in the healthy controls (p=0.03). The between-group differences (including the healthy donors) were statistically significant in the case of HBs and MBs, but not in the case of PPBs and PBs. Only one treated patient showed a transiently large increase in PPBs. There were statistically significant differences in all of the parameters between the untreated patients and those receiving biological therapy, and in some cases between the untreated patients and healthy controls, but never between the controls and the treated patients. Four non-responders to anti-TNF therapy had a smaller number of total circulating B cells than the untreated patients., Conclusions: Anti-TNF drugs disinhibit B cell production in IBD patients, but maintain the constant homeostasis of circulating B cells. The presence of individual variations may allow the activity of anti-TNF drugs to be monitored by studying B cell subgroups., (Copyright © 2017 Elsevier B.V. All rights reserved.)

B lymphocytes express various different types of surface immunoglobulins that are largely unrelated to other hematological lines, although some reports have described a relationship between malignant B cells and other cells such as macrophages. Multiple genes of hematopoietic lineage, including transcription factors, are co-expressed in hematopoietic stem cells and progenitors, a phenomenon referred to as "lineage priming". Changes in the expression levels and timing of transcription factors can induce the lineage conversion of committed cells, which indicates that the regulation of transcription factors might be particularly critical for maintaining hierarchical hematopoietic development. The aim of this study was to evaluate the surface markers of particular IgM-positive and irregularly nucleated cells detected in patients with inflammatory bowel disease (IBD), and to assess their association with diagnosis and inflammatory cell recruitment. Small intestine, colon and rectal biopsy specimens of 96 IBD patients were studied. Immunoglobulin-producing cells (IPCs) were analyzed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The specimens positive for B cells with irregular nuclei were assessed using monoclonal antibodies specific for CD79, and λ and κ chains in order to confirm their B cell nature. CD15+ cells, an important marker of inflammatory cell recruitment, were also evaluated. Statistical correlations were sought between the histological findings and clinical expression. 34 (35.4%) of the 96 patients (64 with ulcerative colitis and 32 with Crohn's disease) presented a periglandial localization of IPCs with irregular nuclei, which showed surface markers specific for the B cell subset, such as IgM and CD79, but quantitative differences in λ and κ chains. These specimens also contained CD15-positive cells, which are usually absent in healthy controls. The quantitative aspects and localization of the CD15-positive cells correlated with the distribution of the IPCs with irregular nuclei. IPCs with irregular nuclei were significantly more frequent in those patients with Crohn's disease than in those with ulcerative colitis (p<0.001). The finding of a subpopulation of cells that simultaneously showed irregular nuclei and B cell markers, such as functional surface IgM, in patients with IBD suggests that an unusual subgroup of B cells that correlates with CD15 expression and a diagnosis of Crohn's disease may be observed in the inflammatory process., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Background: Methotrexate is considered a treatment for Crohn's disease, whilst few data in ulcerative colitis are available., Aim: To evaluate frequency, indications, efficacy and safety of methotrexate in inflammatory bowel disease patients., Methods: 5420 case histories were reviewed., Results: Methotrexate was prescribed to 112 patients (2.1%; 89 Crohn's disease, 23 ulcerative colitis). It was the first-line immunosuppressive option in 32 (28.6%), it was an alternative drug due to toxicity or failure of thiopurines in 80 (71.4%). Steroid-dependence represented the main indication both when it was used as first (13/32, 40.6%) and second option (41/80, 51.2%). Efficacy was considered optimal in 39/112 (34.8%), partial in 29/112 (25.9%), absent in 22/112 (19.6%), not assessable in 22/112 (19.6%). Side effects happened in 49 out of 112 patients (43.7%) (39 Crohn's disease, 10 ulcerative colitis), leading to drug discontinuation in 38 (33.9%). The occurrence of side effects was approximately fivefold higher in patients who did not receive folic acid (14/19, 73.7%) than in those who did (35/93, 37.6%): odds ratio 4.64, 95% confidence interval 1.54-14.00; p=0.005., Conclusions: The use of methotrexate appears to be negligible in clinical practice. However, our results suggest that, if appropriately used, methotrexate could be more widely administered to inflammatory bowel disease patients with complicated disease., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Inflammatory bowel disease (IBD) is thought to be due to an abnormal interaction between the host immune system and commensal microflora. Within the intestinal immune system, B cells produce physiologically natural antibodies but pathologically atypical anti-neutrophil antibodies (xANCAs) are frequently observed in patients with IBD. The objective is to investigate the localisation of immunoglobulin-producing cells (IPCs) in samples of inflamed intestinal tissue taken from patients with IBD, and their possible relationship with clinical features., Methods: The IPCs in small intestinal, colonic and rectal biopsy specimens of patients with IBD were analysed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The B cell phenotype of the IPC-positive samples was assessed using monoclonal antibodies specific for CD79, CD20, CD23, CD21, CD5, λ and κ chains. Statistical correlations were sought between the histological findings and clinical expression., Results: The study involved 96 patients (64 with ulcerative colitis and 32 with Crohn's disease). Two different patterns of B lymphocyte infiltrates were found in the intestinal tissue: one was characterised by a strong to moderate stromal localisation of small IgM+/CD79+/CD20-/CD21-/CD23-/CD5± IPCs (42.7% of cases); in the other (57.3%) no such small IPCs were detected in stromal or epithelial tissues. IPCs were significantly less frequent in the patients with Crohn's disease than in those with ulcerative colitis (p = 0.004)., Conclusion: Our findings suggest that different immunopathogenetic pathways underlie chronic intestinal inflammation with different clinical expressions. The presence of small B lymphocytes resembling B-1 cells also seemed to be negatively associated with Crohn's disease. It can therefore be inferred that the gut contains an alternative population of B cells that have a regulatory function.

We descrive the case of a patient with inflammatory bowel disease complicated by erythema nodosum and anti PR3 positivity. The patient was exposed to two different bacteria: salmonellosis was reported in patient history, while Staphylococcus aureus infection was diagnosed during the present hospital stay. Antibiotics and steroids are effective.

Background: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are intestinal diseases perceived differently by patients and doctors: the former is considered essentially as an 'organic' disease (i.e. an illness in which the role of stress or psychological factors is at best secondary to the disease itself), whereas the latter is acknowledged as a 'functional' disorder (i.e. illness thought to be more in the 'mind' than in the body of the patient). Accordingly, the respective impact of the two diseases on patients' health-related quality of life (HRQOL) is perceived to be very different. We aimed to compare the relative impact of the disease on HRQOL, psychological profile and perceived burden of stressful life events in two groups of outpatients suffering from IBS and IBD and attending our outpatient department at an Italian university hospital. Eighty patients with IBD (26 with ulcerative colitis and 54 with Crohn disease) and 85 controls with IBS formed the patient samples of the study., Methods: Three questionnaires were given to the patients while they were attending the outpatient department because of their previously diagnosed disease, namely the SF-36 (a generic well-validated tool for measuring HRQOL), the SCL-90 (for assessing the psychological profile of patients), and the Holmes & Rahe schedule (for the assessment of stressful life experiences). The results were then compared by means of analysis of variance (ANOVA) and Bonferroni-adjusted t test, when appropriate., Results: HRQOL appeared to be similarly reduced in both disease groups (SF-36 overall mean value: 58.2 +/- 16.1 in IBS patients versus 56.4 +/- 22.3 in IBD patients: P > 0.05) in comparison with normative Italian data. Furthermore, the overall severity of psychological symptoms was not statistically different between patients suffering from IBD versus IBS, as shown by SCL-90 mean scores of 0.89 + 0.45 versus 0.83 +/- 0.48, respectively (P > 0.05). On the contrary, the severity of recent stressful life experiences was perceived to be higher by IBS than by IBD patients (mean SRE score: 110.8 = 110.2 versus 61.6 +/- 78.8; P < 0.05)., Conclusion: Our study supports the notion that, at least in referral centres, patients with IBS show health-related quality of life, psychological distress and recent occurrence of stressful life events of severity at least comparable with age-matched IBD patients.

The aetiology of inflammatory bowel disease remains unknown, but genetic, immuno-inflammatory, infectious, vascular and neural factors play an important role. All effective treatments in use today were introduced empirically and most have multiple action. Targeted therapy is very attractive, either with cell and gene therapy or by using specific cytokine inhibitors and inhibitory cytokines. The role of the intestinal milieu, and enteric flora in particular, appears to have a much greater significance than previously appreciated. The reduction of any changes leading to pro-coagulant activity may be a promising line of therapeutic investigation, and measures to reduce platelet aggregation and endothelial cell adhesiveness are examples of therapeutic potentials. Finally, there has been tangible demonstration of the ability of nerves to alter the inflammatory process which will lead to new therapeutic approaches in inflammatory bowel disease.

Background: Although a reduced prevalence of Helicobacter pylori infection has been observed in inflammatory bowel disease (IBD) patients, the clinical significance of H. pylori infection in this setting remains unknown. The aim of this study was, therefore, to evaluate the prevalence of H. pylori infection in a large series of IBD patients and the frequency of gastroduodenal lesions in those who agreed to undergo upper GI endoscopy., Methods: Two hundred and sixteen consecutive IBD patients (123 with Crohn's disease (CD) and 93 with ulcerative colitis (UC)) had their anti-H. pylori IgG titres measured. Two hundred and sixteen blood donors matched for age, sex, place of birth in Italy, and socioeconomic status served as controls. All patients were offered the possibility of undergoing endoscopy with antral and corpus biopsies regardless of their H. pylori status., Results: The overall seroprevalence of H. pylori infection was 48% in IBD patients versus 59% in the control group (P < 0.05), with a significantly lower frequency in CD versus UC patients (41% versus 56%). After adjustment for age, education, and socioeconomic status CD remained associated with a significantly lower risk of H. pylori infection. Previous therapy with sulphasalazine but not with 5-aminosalicylic acid or with steroids/immunosuppressants was associated with a reduced risk of H. pylori infection both in CD and UC patients. One hundred and eighty-nine patients (110 with CD and 79 with UC) underwent endoscopy; the prevalence of peptic ulcer was similar in both groups (5.5% in CD and 5.1% in UC patients); however, 11 more CD patients had gastroduodenal ulcers that were interpreted as CD-related; 7 of these patients had never had foregut symptoms. Two CD patients had granulomatous gastritis at histology, and another 16 patients with CD had H. pylori-negative gastritis., Conclusions: IBD patients have a reduced prevalence of H. pylori infection as compared with matched healthy controls; this appears mostly attributable to a reduced frequency of H. pylori colonization in CD patients. Previous use of sulphasalazine is associated with a reduced risk of infection both in CD and UC patients. Of CD patients 10% have a gastroduodenal localization of their disease, which is often asymptomatic. Of CD patients 15% also have H. pylori-negative gastritis at histology.