Fenton Schaffner

Autoantibodies against integral membrane proteins of the nuclear envelope in patients with primary biliary cirrhosis

BACKGROUND/AIMSnAutoantibodies against nuclear membrane proteins have been identified in patients with primary biliary cirrhosis (PBC). The aim of the present study was to determine the incidence of these autoantibodies in patients with PBC and examine their significance.nnnMETHODSnAn assay using recombinant polypeptides was designed to unequivocally detect autoantibodies against gp210 and the lamin B receptor, integral proteins of the nuclear membranes.nnnRESULTSnAutoantibodies against gp210 were detected in 15 of 159 patients with PBC and 0 of 46 controls. Autoantibodies against lamin B receptor were detected in 2 patients with PBC and 0 controls. The presence of these autoantibodies had a sensitivity of 11% and specificity of 100% for the diagnosis of PBC. Autoantibodies against gp210 were present in 4 of 19 (21%) patients with PBC who did not have detectable antimitochondrial antibodies. Patients with PBC and gp210 autoantibodies had a higher incidence of associated arthritis.nnnCONCLUSIONSnAutoantibodies against gp210 and the lamin B receptor are present in approximately 10% of patients with PBC. These autoantibodies are highly specific for the diagnosis of PBC and may be useful in diagnosing individuals without antimitochondrial antibodies and in identifying a subgroup of patients with an increased incidence of associated arthritis.

Hypertrophic, hypoactive smooth endoplasmic reticulum: a sensitive indicator of hepatotoxicity exemplified by dieldrin.

Rats with hypertrophic smooth endoplasmic reticulum (ER) and increased activities of the drug-handling enzymes induced by dieldrin were stressed with larger doses of the pesticide. The activity of the drug-handling enzymes was thus reduced, but liver weight, smooth ER, and P-450 hemoprotein remained elevated. While no changes were apparent by light microscopy, the hypertrophic, hypoactive smooth ER was recognized as tight clusters of tubular membranes associated with abnormalities of the mitochondrial membrane. Similar but not identical morphologic changes were noted in human liver diseases associated with hepatic insufficiency. Hypertrophic, hypoactive smooth ER may indicate transition from adaptation of injury, and can be used as a sensitive parameter of toxicity.

Chronic cholestasis in hepatic sarcoidosis with clinical features resembling primary biliary cirrhosis: Report of two cases

Two cases of sarcoidosis with predominantly hepatic involvement are reported, both with the gradual development of progressive jaundice and other clinical features of primary biliary cirrhosis without immunologic or morphologic evidence of that disease. The autopsy findings in one case are described.

Ultrastructural features of canine hepatic auxiliary transplant rejection.

Abstract Auxiliary canine hepatic homografts were examined electron microscopically 24 hours to 17 days after transplantation. Many nonspecific changes were present. Early, the endoplasmic reticulum was dilated and the mitochondria were abnormal. After the initial postoperative period, autophagic vacuoles, shedding of cytoplasm, light and dark cells, and acidophilic bodies were present and macrophages were common. Initial ischemic cell injury can be explained by vascular derangements inherent in the process of transplantation. Its persistency may result from impaired perfusion by excess mesenchymal cells in sinusoids and tissue spaces and by competition between these and hepatocytes for nutrients. An immunologic component is suggested by the presence of large mononuclear cells, with many ribosomes seen in delayed type hypersensitivity reactions. These were closely approximated to and indenting the hepatic parenchymal cells, but bridging between the mesenchymal cells or hepatocytes was not found. The similarity of the mesenchymal cells and their relation to hepatocytes in chronic active hepatitis in man supports the idea that in both transplant rejection and in the human disease an immunologic process mediated by cells adds to the destruction of hepatic tissue.

Diagnostic criteria of autoimmune chronic liver disease

To The Editor: We read with interest the article by Lebovics and colleagues on autoimmune chronic active hepatitis in postmenopausal women (Digestive Diseases and Sciences 30:824-828, 1985). The authors report a very poor response to steroid treatment and a bad prognostic significance of antinuclear antibodies (ANA) (not of anti-smooth-muscle antibodies, SMA) in their retrospectively examined series. In our opinion, the crucial point is whether Lebovics patients can be reliably regarded as having autoimmune liver disease. More generally, we want to focus the attention on the relevance of conventionally detected ANA and SMA as the only positive standard usually considered for such a diagnosis. A titer equal to or higher than 1:40 is indeed currently regarded as the diagnostic cut off for either ANA or SMA (1), but no threshold is mentioned when both antibodies are present in the same serum. This sort of bonus effect, although irrelevant with respect to the results of the study, has no clear-cut rationale and has never been reported, as far as we know, in the literature. Besides the titer, a better characterization of both ANA and SMA, as it can be reached by the indirect immunofluorescence (1FL) test using new rheumatological substrates like HEp-2 cells, can be important in terms of diagnostic value. We have reported that, among the IFL ANA patterns, the homogeneous (ANA-H) is associated with autoimmune liver disease (2); of the SMA reactivities, as well, antibodies to cytoskeletal actin-containing micro filaments (anti-MF) have been demonstrated to identify autoimmune cases (3). A summary of our results is reported in Table 1. It is apparent that, if a diagnostic significance is attributed to ANA-H and anti-MF instead of crude ANA and SMA, respectively, the number of autoimmune cases halves (from 45 to 24) and that of ANAand/or SMA-positive patients with disease of other etiology markedly decreases (from 30 to 5). As the rule, the reduction in sensitivity is counterbalanced by the gain in specificity. Further studies are required to assess the reliability of such a diagnostic rearrangement. It must be pointed out that the detection of autoimmune phenomena does not necessarily imply the presence of an autoimmune disease; in this perspective, and in the absence of a golden reference standard, we do believe that a correct definition of autoimmune chronic liver disease should take into account both immunogenetic data (as the prevalence of HLA-DR3 haplotype) (4) and the assessment of an autoimmune involvement of other organs, which, although clinically rare, should not be overlooked. FABIO CASSAN1, MD MARCO FUSCOM, MD LAURA BAFFONI , MD UM~ERTO VOLTA, MD MARCO LENZI, MD FRANCESCO B. BIANCHI, MD EMILIO PISI, MD