Autoantibodies to beta tubulin in autoimmune liver diseases - relation to pANCA and clinical relevance.

There was evidence that pANCA (perinuclear antineutrophil cytoplasmic antibodies) in autoimmune liver diseases react with human beta-tubulin-5 (TBB5). Here we re-evaluate the specificity and clinical relevance of anti-TBB5 antibodies. Patients with untreated autoimmune hepatitis (AIH; n=53), AIH under immunosuppressive therapy (AIH-IS; n=125), primary sclerosing cholangitis (PSC; n=40), primary biliary cholangitis (PBC; n=250), non-autoimmune liver diseases (n=158), inflammatory bowel diseases (IBD; n=30), and healthy individuals (n=62) were tested by enzyme linked immunosorbent assay (ELISA) for IgG- and IgA-antibodies against recombinant human TBB5. pANCA were detected by immunofluorescence test. Sera were absorbed with TBB5 coupled to cyanogen bromide-activated sepharose. Prevalence and reactivity of IgG anti-TBB5 were significantly higher in patients with untreated AIH (68%; arbitrary units [AU] median:369) than in PSC (28%; AU median:84, p<0.001), other liver diseases (14%; AU median:185, p<0.0001), IBD (3%; AU median:111, p<0.0001) and healthy controls (3%; AU median:135; p<0.0001). Anti-TBB5 did not correlate with pANCA, and immunoprecipitation with TBB5 did not abolish pANCA reactivity. In untreated AIH anti-TBB5-reactivity was significantly higher than in AIH-IS. Transaminases decreased under IS preferentially in anti-TBB5 negative patients. There was no correlation between anti-TBB5-reactivity and histological stages. IgA-anti-TBB5 was mainly found in alcohol-associated liver disease (ALD; 39%). Our data do not support TBB5 as an autoantigenic target of pANCA. However, IgG-anti-TBB5 showed high specificity for (untreated) AIH. While they did not correlate with histological and laboratory parameters, their presence may indicate a poor response to IS.

Human Intervention Study: Alkylresorcinol Metabolites as Potential Biomarkers for Grain Intake and the Occurrence of Alkylresorcinols in Commonly Consumed Foods in the German Retail Sector.

Grains are one of the primary nutrients and are associated with many health benefits. To reflect the intake of grain-based products, two promising potential biomarkers are alkylresorcinol (AR) metabolites 3,5-dihydroxybenzoic acid (3,5-DHBA) and 3-(3,5-dihydroxyphenyl)-propanoic acid (3,5-DHPPA). The aim of this study was to validate the occurrence of AR in food samples and investigate the suitability of their metabolites as potential biomarkers in human intervention studies. In the first step, the AR content in different grain products from the German retail sector was analyzed by GC-MS. ARs were found in higher concentrations in whole grain products and in moderate contents in refined grains and quinoa. Based on these results, human intervention studies were performed in the next step, and the AR metabolites 3,5-DHBA and 3,5-DHPPA were analyzed by LC-MS/MS in urine samples. The intake of only whole grain products leads to an increasing level of both potential biomarkers, while a refined grain diet shows decreasing levels of the AR metabolites. The excretion of 3,5-DHBA after a whole grain-rich diet differs significantly (p = 0.043) from no grain intake.