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.