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Background-Butyrate oxidation within the colonocyte is selectively inhibited by hydrogen sulphide, reproducing the metabolic lesion observed in active ulcerative colitis. Aims-To study generation of hydrogen sulphide by sulphate reducing bacteria (SRB) and the eVects of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis in order to identify a role of this noxious agent in pathogenesis. Patients-Fresh faeces were obtained from 37 patients with ulcerative colitis (23 with active disease) and 16 healthy controls. Methods-SRB were enumerated from fresh faecal slurries and measurements made of sulphate reducing activity, and sulphate and hydrogen sulphide concentrations. The eVect of 5-ASA on hydrogen sulphide production was studied in vitro. Results-All controls and patients with active ulcerative colitis carried SRB and total viable counts were significantly related to the clinical severity grade. SRB were of two distinct types: rapidly growing strains (desulfovibrios) which showed high sulphate reduction rates, present in 30% of patients with ulcerative colitis and 44% of controls; and slow growing strains which had little activity. In vitro, 5-ASA inhibited sulphide production in a dose dependent manner; in patients with ulcerative colitis not on these drugs faecal sulphide was significantly higher than in controls (0.55 versus 0.25 mM, p=0.027). Conclusions-Counts and carriage rates of SRB in faeces of patients with ulcerative colitis are not significantly diVerent from those in controls. SRB metabolism is not uniform between strains and alternative sources of hydrogen sulphide production exist in the colonic lumen which may be similarly inhibited by 5-ASA. The evidence for hydrogen sulphide as a metabolic toxin in ulcerative colitis remains circumstantial. (Gut 2000;46:64-72)

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

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Aims-To compare and contrast the sensitivity, specificity, and positive predictive values of IgA antibodies to guinea pig tissue transglutaminase (ELISA), endomysium, and reticulin (immunofluorescence), and gliadin (ELISA), and IgG antibodies to gliadin and tissue transglutaminase. Methods-Sera from 27 newly diagnosed patients with coeliac disease, 65 biopsied gastrointestinal disease controls, and 50 consecutive blood donors were tested. All cases were adults. Results-IgA anti-tissue transglutaminase showed a sensitivity of 85% (23/27 coeliac disease cases seropositive), specificity 97% (2/65 controls and one blood donor showing low titre positivity), and a positive predictive value of 92%. High titre anti-tissue transglutaminase was only seen in coeliac disease. Disease controls with mucosal damage unrelated to gluten enteropathy were IgA anti-tissue transglutaminase negative. Sensitivity, specificity, and positive predictive values for IgA anti-endomysial antibody (monkey oesophagus) were 100%, 100%, and 100%, respectively, and for IgA anti-gliadin, 93%, 95%, and 89%, respectively. Conclusions-Tissue transglutaminase is a major autoantigen in coeliac disease. IgA (but not IgG) anti-tissue transglutaminase, especially when in high titre, is closely associated with coeliac disease, but low titres may not be disease specific. In this small pilot study, the established IgA anti-endomysial assay was the superior test. (J Clin Pathol 1999;52:274-277)