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IL-9, which may be an inflammatory or regulatory cytokine, can be experimentally produced in a Th17 or modified Th2 context in the presence of T cell receptor (TCR) stimulation. The primary aim of this study was to measure serum IL-9 levels in patients with inflammatory bowel disease (IBD), and evaluate their relationships with the patients' clinical characteristics. The secondary aim was to determine the levels of interferon-γ (IFN (interferon)-γ), Th2 cytokines (IL-4, IL-5 and IL-13), and IL-6 in order to clarify the context of detectable peripheral cytokines in which IL-9 is produced.Venous blood samples of 43 IBD patients (20 with Crohn's disease [CD] and 23 with ulcerative colitis [UC]) were analysed by means of quantitative enzyme-linked immunosorbent assays using purified anti-human IL-4, IL-5, IL-13, IFN-γ, IL-9 and IL-6 antibodies, and the laboratory findings were statistically correlated with their clinical expression.None of the patients showed the peripheral presence of IL-4, IL-5 and IL-13. Forty (93%) were positive for IFN-γ, thus confirming the presence of Th1 in both UC and CD, and IFN-γ levels correlated with disease activity (P = 0.045). Eighteen patients (41%) were positive for IL-9, which was associated with a severe prognosis (P <0.001), and 72.2% of the IL-9-positive patients were also IL-6 positive. There was a significant correlation between disease severity and IL-9 in the CD patients (P <0.001), but not in the UC patients (P = 0.1).Our findings confirm the presence of common Th1 cytokines in UC and CD. However the IL-9 positivity indicates the presence of an alternative population of T cells that respond to antigen stimulation and condition the prognosis of IBD. The fact that the same serum IL-9 levels were differentially associated with clinical measures of CD and UC activity suggest that the same cytokine can be produced in different contexts.

BackgroundInflammatory 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.MethodsThe 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.ResultsThe 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).ConclusionOur 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.

BackgroundWe have recently investigated the localisation of immunoglobulin-producing cells (IPCs) in inflamed intestinal tissue samples from patients with inflammatory bowel disease (IBD), and identified two main patterns of B lymphocyte infiltration: one characterised by the moderate strong stromal localisation of small B1 cell-like IgM+/CD79+/CD20-/CD21-/CD23-/CD5 ± IPCs, and the other by the peri-glandular localisation of IPCs with irregular nuclei that had surface markers specific for a B cell subset (IgM and CD79), but quantitative differences in their λ and κ chains. The same patients were also tested for CD15+ receptors, which were localised on inflammatory cell surfaces or in the crypts of the intestinal epithelium. CD15+ receptor distribution in inflamed tissues was limited to the cell structures. The aim of the study was to analyse variations in IPCs and CD15+ cell morphology or distribution in bowel biopsy specimens taken from patients with pre-malignant polyps or adenocarcinomas.MethodsIPCs were analysed by means of immunofluorescence using polyclonal goat anti-human μ chains. The pre-malignant polyp specimens were tested for B cell surface phenotype λ and κ chains, CD79, CD20, CD21 and CD23 using an immunoperoxidase method. CD15+ cells were evaluated using the immunoperoxidase method and monoclonal anti-CD15 IgM.ResultsThe study involved 14 patients (four with pre-malignant polyps and 10 with colorectal adenocarcinomas). The distribution of μ chains and CD15 markers varied in all of the biopsies, but delineated normal cell structures in the pre-malignant polyp specimens. B cell surface phenotype analysis of μ chain-positive cells identified a subset of CD79+/CD20-/CD21-/CD23- IPCs. The IPCs in certain areas showed the sporadic disintegration of inflammatory cell membranes or the accumulation of fluorescence in individual cells. IPC membrane disintegration was particularly marked in all of the adenocarcinoma samples, in which the CD15 markers also showed epithelial cell involvement. Furthermore, six of the ten adenocarcinoma samples had atypical and reorganised membranes that expressed an excess of both receptors and isolated small portions of tissue within the tumour.ConclusionThe findings of this preliminary morphological study suggest the presence of membrane disintegration and remodelling mechanisms in the tumours. The newly-formed membranes expressed high concentrations of inflammatory cell receptors that can confer adhesive properties.

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.

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Dear Editor, We read with great interest the paper by Lam and Lau, 1 which recently appeared on your journal. In their paper, the authors report about two patients with a large number (52 and 147, respectively) of fundic gland polyps (FGPs) without any known association with previous therapies or genetic familial syndromes, which they aptly named "idiopathic" (literally "without known cause") multidinous FGPs.FGPs are small sessile polyps (2-3 mm), usually multiple, of the acid-secreting gastric mucosa. They are characterized by shortened gastric pits and cystic dilations, both superficial and deep, bordered by columnar mucous, chief, and parietal cells. They are almost always negative for Helicobacter pylori colonization. 2 Although they show the same histology, they have been described as sporadic, 3 associated with familial adenomatous polyposis (FAP), 4 attenuated FAP, 5 Zollinger-Ellison syndrome, 6,7,8 MUTYH-associated polyposis, 9 gastric adenocarcinoma and proximal polyposis of the stomach (GAAPS), 10,11 and absorptive hypercalciuria 12 (Fig. 1). Although recently K} ov ari et al. 13 described subtle differences between sporadic, FAP-associated, and GAAPS-associated FGPs, so far the only difference between the histology of fundic polyps has been in the frequency of dysplasia, which is rare in sporadic FGPs (1%), frequent in FAP-associated polyps (30-50%), and almost universal in GAAPS-associated polyps.Lam and Lau 1 were clearly faced with a management dilemma-how to treat such unusual patients. They never received a long-term treatment with proton pump inhibitors (if such a treatment promotes polyps at all), nor had a positive family history for genetic syndromes with a known risk for FGP development. In absence of clear guidelines for such a situation, the authors decided to endoscopically remove all polyps and to submit them to histologic examination. Quite surprisingly, not a single polyp showed dysplasia.Given such results, we would suggest to Lam and Lau to submit their polyps to molecular biology examination, in a search for possible new mechanisms driving such an exceptional multidinous polyposis.