Recent evidence implicates adaptive immunity as a key player in the mechanisms supporting hepatic inflammation during the progression of nonalcoholic fatty liver disease (NAFLD). In these settings, patients with NAFLD often show an increase in the circulating levels of antibodies against oxidative stress-derived epitopes (OSE). Nonetheless, the actual role of humoral immunity in NAFLD is still unclear. This study investigates the contribution of B-lymphocytes to NAFLD evolution. B-lymphocyte immunostaining of liver biopsies from NAFLD patients showed that B-cells were evident within cell aggregates rich in T-lymphocytes. In these subjects, B/T-lymphocyte infiltration positively correlated with both circulating IgG targeting oxidative stress-derived epitopes (OSE) and interferon-γ (IFN-γ) levels. Furthermore, high prevalence of lymphocyte aggregates identified patients with more severe lobular inflammation and fibrosis. In mouse models of NAFLD, the onset of steatohepatitis was characterized by hepatic B2-lymphocytes maturation to plasma cells and by an elevation in circulating anti-OSE IgG titers. B-cell responses preceded T-cell activation and were accompanied by the up-regulation in the hepatic expression of B-cell Activating Factor (BAFF). Selective B2-cell depletion in mice over-expressing a soluble form of the BAFF/APRIL receptor Transmembrane Activator and Cyclophilin Ligand Interactor (TACI-Ig) prevented plasma cell maturation and Th-1 activation of liver CD4 T-lymphocytes. Furthermore, TACI-Ig mice showed milder steatohepatitis and a decreased progression to fibrosis. Similarly, mice treatment with the BAFF-neutralizing monoclonal antibody Sandy-2 prevented hepatic B2-cell responses and ameliorated steatohepatitis. From these data we conclude that B2-lymphocyte activation is an early event in NAFLD evolution and contributes to the disease progression through the interaction with T-cells. Furthermore, combined clinical and experimental data suggest that elevated circulating anti-OSE IgG can identify a subset of NAFLD patients in whom adaptive immunity has a relevant role in the disease evolution toward fibrosis.

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BACKGROUND: Despite the well-known risk of osteoporosis and bone fractures among patients with inflammatory bowel diseases, the WHO FRAX tool has been used in a limited number of studies in this specific population. The purpose of this study was to search for predictors of risk of fractures assessed by FRAX score. METHODS: We prospectively calculated FRAX score for hip and major osteoporotic fractures in inflammatory bowel disease patients consecutively recruited. RESULTS: The mean risk of hip fractures at 10 years, for the 80 recruited patients, resulted 1.4%, while the mean risk of major osteoporotic fractures was 7.8%. The risk of hip fractures was 1.3% among the 30 Crohn's disease patients versus 1.4% (p = 0.82) among 50 ulcerative colitis patients. A prolonged use of corticosteroids correlated with a tendency to a greater risk of hip fracture (r = 0.38, p = 0.08). Patients with normal erythrocyte sedimentation rate (ESR) values had a risk of osteoporotic hip fractures of 0.75%, while those with high ESR values had a risk of 1.86% (p = 0.04). Regarding the risk of major bone fractures, patients with normal ESR values had a risk of 5.9%, versus a risk of 18% in those with elevated ESR (p = 0.03).CONCLUSIONS: The correlation between increase of inflammatory markers and increased risk of osteoporotic fractures and the lack of difference between Crohn's disease and ulcerative colitis suggest a central role of inflammation over malabsorption in this population.

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Background Inflammatory bowel disease (IBD), including Crohn’s disease (CD), ulcerative colitis (UC) and undetermined IBD (IBD-U), are autoimmune chronic remittent diseases affecting the gut. On the other hand celiac disease (CeD) is a gluten related disorder leading to duodenal villous atrophy. Lately, the link between CeD and IBD has become of growing interest. Indeed, CeD prevalence among IBD population has been widely investigated, as well as IBD prevalence in CeD population. Particularly, IBD seems to have a significantly higher prevalence among CeD population than in general population and CeD seems to be more prevalent in IBD population. However, there is still lack of data on whether CeD can influence IBD outcome. So, primary outcome of our study is to measure prevalence of CeD among IBD population and secondary outcome is to evaluate possible influence of CeD on IBD outcome. Methods Data were collected from march 2020 to September 2020 from IBD internal registry in San Giovanni Antica Sede Hospital in Turin. To detect CeD patients, all patients were screened and the ones with a reported duodenal lesion were selected. From those, the ones with defined diagnosis of CeD (presence of serum IgA antitransglutaminase and or IgA anti endomisial antibodies) were finally selected. Prevalence of CeD among IBD was compared to that of general population basing on literature. Then 76 patients were randomly selected as control group, in roder to investigate secondary outcome. To define IBD as complicated Siegel’s score was used (1 out of five item needed to define complicated disease). Results Among 5732 IBD patients we detected 80 patients with duodenal lesions, of whom 27 were diagnosed with CeD. So, prevalence of CeD among our population is about 0,49% whiich is similar to that of general population (0,48%, P=0.98). No differences were found in CeD prevalence among CD, UC and IBD-U subgroups. As regards secondary outcome, in case group complicated IBD was 44,4% while among control group 26,3% (p=0.08). In a mean follow up time of 133,93 months, mean time from diagnosis to complication of IBD was 58,2 months in case group and 102,7 months in control group. As shown in figure 1, Kaplan-Maier curve for event free survival comparing the two groups shows a significant difference between CeD + IBD patients and IBD only patients (p=0,002). Conclusion Even though the retrospective nature of the study could lead to underestimate CeD diagnosis, among our cohort of IBD patients CeD prevalence seems not to be significantly higher than among general population. Despite of that, when associated to CeD, IBD seems to have earlier complications, so these patients may deserve a top down therapeutical approach and/ or a more strict follow up.