In Vivo and in Vitro Binding of IgA to the Plasma Membrane of Hepatocytes

Abstract

IgA bound in vivo was shown by immunofluorescence on the plasma membrane of isolated hepatocytes from subjects with normal liver and patients with liver cirrhosis, chronic active hepatitis or fatty liver. IgA in sera with elevated IgA concentrations, especially from cases with alcoholic cirrhosis, was bound in vitro to isolated hepatocytes from rabbit and mouse. This was not due to the high IgA concentration per se. Moreover, polyclonal polymeric serum-type and secretory IgA, and three of ten polymeric monoclonal IgA preparations, showed similar binding properties. Conversely, purified polyclonal and monoclonal monemeric IgA did not show affinity for the hepatocytes. The binding of polymeric IgA did not seem to depend on the proportion of dimers and larger polymers, kappa- or lambda-type light chains, heavy-chain subclasses, content of J chain or affinity for secetory component. The in vivo binding of IgA by hepatocytes is probably a physiological phenomenon which in part may explain the normal clearance of polymeric IgA from serum.

Changes in size, subclass, and metabolic properties of serum immunoglobulin A in liver diseases and in other diseases with high serum immunoglobulin A.

“…The changes in circulating p-IgA concentrations and FCR found in parenchymal LD but not in B Obst, suggest that the human liver may play a role in the selective removal of plasma p-IgA, but by another mechanism than the SCdependent bile duct cell transport into bile. Such a different, SC-independent mechanism would agree with the reported affinity of human hepatocytes for p-IgA but not for m-IgA, independently of the presence of SC on the hepatocyte (48). The existence and nature of another putative receptor for p-IgA than SC on the human hepatocyte require further study.…”

“…Our present lack of serum p-IgA increase in human B Obst, unlike in rats and rabbits in which B Obst results in a 10 times (or larger) increase in serum p-IgA (45,46), is thus another argument for major species differences in hepatic transport of p-IgA into bile. It is likely that these species differences reflect differences in tissue distribution of SC in the liver: in human liver, SC was detected immunohistochemically only in and on bile duct cells (47,48),2 unlike its clearcut demonstration in and on rat and rabbit hepatocytes (49)(50)(51). Accordingly, the SC-dependent biliary transport of p-IgA in humans is probably restricted to bile duct cells.…”

Selective transport of polymeric immunoglobulin A in bile. Quantitative relationships of monomeric and polymeric immunoglobulin A, immunoglobulin M, and other proteins in serum, bile, and saliva.

“…The finding of FSC in normal bile as well as in bile of an IgA-deficient subject (45) (47). However, in contrast to Nagura et al (26) and others (27), another group (28) found intrahepatocyte SC and IgA, using amplified immunoperoxidase techniques but surprisingly, they found less SC and IgA staining in bile duct cells. In addition, a particular relationship between SC and hepatocytes was suggested by the rapid fall of the high serum SC concentration observed in patients with acute hepatitis when fulminant massive parenchymal necrosis occurred (48).…”

“…(26) also measured the concentration of IgG, IgA, and IgM in hepatic bile, but not in serum, and found predominantly 11S sIgA in bile with virtually undetectable IgG and IgM. They presented elegant immunohistochemical evidence for a SC-mediated endocytotic transport of p-IgA across the biliary epithelium, and like others (27), could not demonstrate SC on and in hepatocytes, despite positive results of another group (28).…”

Detection of immunoglobulins G and A on the cell membrane of hepatocytes from patients with alcoholic liver disease.

“…Its restriction to active or inactive cirrhosis and the granular appearance of the antibody deposition represent an intriguing observation. The finding could be related to the increase of circulating IgA dimers complexed with intestinal antigens, previously reported in alcoholic cirrhosis.24 25 The precise delineation of putative antigen(s) for the membrane-bound antibodies and the possible pathogenetic role for IgG and IgA in producing liver cell injury will be sought in further experiments involving elution of these antibodies. * * * *…”