Cytotoxic T cell (CTL) activation by antigen requires the specific detection of peptide-major histocompatibility class I (pMHC) molecules on the target-cell surface by the T cell receptor (TCR). We examined the effect of mutations in the antigen-binding site of a Kb-restricted TCR on T cell activation, antigen binding and dissociation from antigen.These parameters were also examined for variants derived from a Kd-restricted peptide that was recognized by a CTL clone. Using these two independent systems, we show that T cell activation can be impaired by mutations that either decrease or increase the binding half-life of the TCR-pMHC interaction. Our data indicate that efficient T cell activation occurs within an optimal dwell-time range of TCR-pMHC interaction. This restricted dwell-time range is consistent with the exclusion of either extremely low or high affinity T cells from the expanded population during immune responses.

Both LFD and LGG are efficatious in patients with IBS.

Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

These data suggest that a diet low in FODMAPs is an efficacious treatment solution in the management of functional bowel symptoms for IBS and IBD patients.

AIMTo investigate the effect of a low-FODMAP diet on irritable bowel syndrome (IBS)-like symptoms in patients with inflammatory bowel disease (IBD).METHODSThis was a randomised controlled open-label trial of patients with IBD in remission or with mild-to-moderate disease and coexisting IBS-like symptoms (Rome III) randomly assigned to a Low-FODMAP diet (LFD) or a normal diet (ND) for 6 wk between June 2012 and December 2013. Patients completed the IBS symptom severity system (IBS-SSS) and short IBD quality of life questionnaire (SIBDQ) at weeks 0 and 6. The primary end-point was response rates (at least 50-point reduction) in IBS-SSS at week 6 between groups; secondary end-point was the impact on quality of life.RESULTSEighty-nine patients, 67 (75%) women, median age 40, range 20-70 years were randomised: 44 to LFD group and 45 to ND, from which 78 patients completed the study period and were included in the final analysis (37 LFD and 41 ND). There was a significantly larger proportion of responders in the LFD group (n = 30, 81%) than in the ND group (n = 19, 46%); (OR = 5.30; 95%CI: 1.81-15.55, P < 0.01). At week 6, the LFD group showed a significantly lower median IBS-SSS (median 115; inter-quartile range [IQR] 33-169) than ND group (median 170, IQR 91-288), P = 0.02. Furthermore, the LFD group had a significantly greater increase in SIBDQ (median 60, IQR 51-65) than the ND group (median 50, IQR 39-60), P < 0.01.CONCLUSIONIn a prospective study, a low-FODMAP diet reduced IBS-like symptoms and increased quality of life in patients with IBD in remission.

In a pooled analysis of population-based studies, we found age at IBD onset to vary with sex. Further studies are needed to investigate mechanisms of sex differences in IBD incidence.

Background and aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis (UC) in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the five-year outcome and disease course of patients with UC in the Epi-IBD cohort. Methods: In a prospective, population-based inception cohort of unselected patients with UC patients were followed-up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis. Results: A total of 717 patients were included in the study. During follow-up, 43 (6%) patients underwent a colectomy, while 163 (23%) patients were hospitalized. Of patients with limited colitis (distal to the left flexure), 90 (21%) progressed to extensive colitis. In addition, 92 (27%) patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalization (HR: 0.5 CI95% 0.3-0.8). Overall, patients were treated similarly in both geographical regions and 80 (11%) patients needed biological therapy while 210 (29%) patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalization (HR: 0.5 CI95% 0.3-0.8). Conclusions: While patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes including colectomy rates were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalization.

SUMMARY Background