[11] For example, passive transfer of AMA or immunization selleck kinase inhibitor with target antigens of AMA cannot induce the disease in animal models, and reduction of the titers of AMA does not improve the disease.[1] Therefore, some researchers suppose that AMA does not seem to have an etiopathogenic role in PBC. In addition, because these M2 antigens are ubiquitously expressed in almost all cells of the body, AMA does not explain the organ-specificity of PBC.[1] In contrast, it has been proposed that the cross-interaction of AMA with the epitheliocytic antigens of bile cholangioles may damage the epithelium of ductules, resulting in their obliteration.[12]

Cellular immune mechanisms involving T-cell reaction are thought to participate in the pathogenesis of PBC, especially CNSDC and bile duct loss. T-helper 1 type CD4+ T cells expressing γ-interferon or CXCR3 have been check details reported to play important roles in progressive bile duct damage of PBC.[13] Moreover, both CD4+ and CD8+ autoreactive T cells that specifically target PDC-E2 self-antigen, were detected in both peripheral blood and liver tissues of patients with PBC.[14] The presence of anti-M3R antibodies

in patients with PBC should be significant both clinically and pathologically. First, anti-M3R antibodies could be useful as diagnostic markers for PBC. Antibodies reactive to the first loop had the highest diagnostic value for PBC

with moderate sensitivity (73.3%), and with both high specificity (80.0–100.0%) and high accuracy (74.0–84.6%) between PBC and CHC, NASH, PSC, obstructive jaundice, drug-induced liver injury and controls. Moreover, we could raise the sensitivity to 93.3% by analyzing anti-M3R antibodies against at least one epitope. Therefore, the combination of anti-M3R antibodies reactive to these epitopes could be a useful tool for the differential 上海皓元 diagnosis of PBC from CHC, NASH, PSC, obstructive jaundice, drug-induced liver injury and HC. Importantly, all 19 patients with PBC negative for antimitochondria M2 subunit antibody carried anti-M3R antibodies reactive to at least one extracellular domain of M3R, and 17 out of these 19 patients (89.5%) with PBC carried anti-M3R antibodies reactive to the first loop. Thus, anti-M3R antibodies could be useful as a new diagnostic marker for especially AMA negative patients with PBC. Second, we focused on the relationship between anti-M3R antibodies and clinicopathological features of PBC, including histopathological findings and various other autoantibodies. Unfortunately, we could not detect any difference between anti-M3R antibody positive and negative patients with PBC.