Penetration and Co-localization in MDCK Cell Mitochondria of IgA Derived from Patients with Primary Biliary Cirrhosis

Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis

“…Moreover, dual staining of liver sections from PBC patients showed colocalization of IgA and PDC-E2, both cytoplasmically and at the apical surface. 30 Given that salivary epithelial cells secrete IgA into saliva similar to bile duct cells, the high incidence of salivary ductular destruction in patients with PBC, with or without antibody markers unique to Sjogren' s syndrome, 9,24 and our finding of specific IgA-PDC-E2 in PBC patient saliva, we suggest that a process similar to that occurring in the liver could be affecting the salivary glands in these patients.…”

“…29 In the case of PBC, where there is characteristic biliary ductule damage, it has been hypothesized that during IgA transport through bile duct epithelial cells, IgA AMA may bind to mitochondrial antigens, leading to a cytotoxic effect through inhibition of key metabolic pathways or through the accumulation of immune complexes. 30 In fact, it has been shown that during the intracellular transport from periductal tissue into the bile duct lumen, IgA AMA colocalizes with mitochondria in Madine-Darby canine kidney cells transfected with the human IgA receptor. Moreover, dual staining of liver sections from PBC patients showed colocalization of IgA and PDC-E2, both cytoplasmically and at the apical surface.…”

Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis

“…Media consisted of DMEM supplemented with 10% fetal calf serum (FCS). 9,10 The inserts were composed of thin membranes of polyethylene terephthalate with 1.0 m pores, 1.6 ϫ 10 6 pores/cm 2 . The cell cultures were maintained at 37°C with 5% CO 2 in a humid incubator.…”

“…IgA AMAs are readily detected in the bile, saliva, and even the urine of patients with PBC. 6 -8 Previous work involving confocal microscopy studies of Madine-Darby canine kidney (MDCK) cells expressing pIgR 9,10 has demonstrated that AMA IgA co-localizes, and thus potentially interacts with, PDC-E2 in the cytoplasm of these cells. A limitation of the studies to date has been the absence of functional effects of IgA AMAs on pIgR positive cells, due in large part to the difficulty in obtaining enough polymeric IgA.…”

The immunobiology of bile and biliary epithelium

“…Malmborg et al postulated that there may be a direct effect of these autoantibodies on the mitochondrial function of BECs; this colocalization may be linked to the biological alteration of BEC leading to their destruction. 52 PSC, chronic GVHD, and liver allograft rejection are other diseases characterized by lymphocyte-mediated bile duct destruction. As in PBC, aberrant expression of MHC class II, but not B7, by BECs has been shown to occur.…”