5%) with PBC carried anti-M3R antibodies reactive to the first loop. The positivity of anti-M3R antibodies against each extracellular domain, at least one epitope and all four epitopes was comparable between anti-mitochondria M2 subunit antibody positive and negative patients with PBC (Table 3). Table 4 lists the epitopes of anti-M3R antibodies in patients with PBC, CHC, NASH, PSC, obstructive jaundice, drug-induced liver injury and controls. Of the 90 patients with PBC, 84 (93.3%) had anti-M3R

MAPK inhibitor antibodies reactive to at least one B-cell epitope on the M3R, while the other six patients did not have any anti-M3R antibodies. Of the 40 patients with CHC, 31 (77.5%) were positive for anti-M3R antibodies against at least one B-cell epitope, the other nine patients were negative. Of the 21 patients with NASH, 18 (85.7%) were positive for anti-M3R antibodies against at least one B-cell epitope and the other three patients were negative. Seventy percent (7/10) of PSC patients, 100% (14/14) of obstructive jaundice and 100% (10/10) of drug-induced liver injury were also positive for anti-M3R

antibodies against at least one B-cell epitope. In contrast, only four (9.5%) of 42 controls were positive for anti-M3R antibodies against at least one B-cell epitope. Antibodies to one B-cell epitope on the M3R were detected in six patients with PBC out of 84 patients, seven selleck chemicals patients with Cell Cycle inhibitor CHC, three patients with NASH, one patient with PSC, two patients with obstructive jaundice, six patients with drug-induced liver injury and two controls. Antibodies reactive to two B-cell epitopes were detected in 10 patients with PBC, 13 patients with CHC, 15 patients with NASH, one patient with PSC, four patients with obstructive jaundice, four patients

with drug-induced liver injury and one control subject. Twenty-two patients with PBC, eight patients with CHC, three patients with PSC, eight patients with obstructive jaundice and one control subject were positive for antibodies to three B-cell epitopes. In 54.8% (46/84) of patients with PBC, antibodies reactive to all four B-cell epitopes were detected, compared to only three patients with CHC and two patients with PSC, and none of the NASH patients, obstructive jaundice patients, drug-induced liver injury patients and controls. Based on these results, we concluded that anti-M3R antibodies had several B-cell epitopes on the extracellular domains of M3R, and that many patients with PBC, CHC, NASH, PSC, obstructive jaundice and drug-induced liver injury carried anti-M3R antibodies that recognized several extracellular domains of M3R. Especially, 46 of the 90 (51.1%) patients with PBC had anti-M3R antibodies reactive to all four B-cell epitopes.