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A new ribosomal antibody is described in patients with systemic lupus erythematosus which reacts with all tissues from varied species, giving a distinctive immunofluorescence pattern. This can best be distinguished from other known autoantibodies on stomach where it reacts with chief cells and pancreas where exocrine cells are brightly stained. The ribosomal nature of the antigen was demonstrated by absorption of immunofluorescence and complement fixation studies using purified subcellular fractions. The antigen was unaffected by ribonuclease and was destroyed by trypsin, suggesting that it is one of the ribosomal proteins, while previously reported antibodies were mainly directed against ribosomal RNA, RNA-protein complexes, or polynucleotides and hybrids. The present ribosomal antibody is uncommon and occurs in less than 1% of SLE patients; its clinical significance is similar to that of ribosomal precipitins as the patients had renal involvement and several have died. [ABSTRACT FROM AUTHOR]

The sera of 131 patients with anti-liver-kidney microsome antibodies (anti-LKM) detected between 1973 and 1979 in two different laboratories were re-examined. (1) Eighty-six anti-LKM corresponded to the description given by Rizzetto, Swana & Doniach (1973), with a pattern of fluorescence predominating on the 3rd portion of the proximal tubules (P3). This group comprised 45 cases of idiopathic chronic hepatitis or idiopathic cirrhosis and one case of halothane-induced hepatitis. (2) Forty-five anti-LKM gave a different pattern on male mouse liver and male rat kidney: (a) fluorescence was greater on centrolobular than on periportal hepatocytes; (b) the first and second portions of proximal tubules (P1 and P2) predominated over P3; (c) P1 fluorescence was equally intense as P2 and (d) P3 cells were heterogeneous with one cell out of 20 more positive than the rest. Absorption tests confirmed that the corresponding antigen was also present in the liver microsomal fraction. A retrospective clinical study discovered tienilic acid-induced hepatitis in all cases. We suggest naming this new antibody 'anti-LKM2'. [ABSTRACT FROM AUTHOR]

A new immunofluorescence pattern of non-organ- and non-species-specific antibody has been observed in occasional sera. Variations of the fluorescence were found in different species. Recognition of the new pattern was particularly characteristic in rat organs (liver: the hepatocytes showed intense roughly granular fluorescence evenly distributed in the cytoplasm; kidney: the bright fluorescence of the first portion of the proximal tubules contrasted with the negative aspect of the other portions of the tubules; stomach: only some cells probably corresponding to the APUD system were positive; pancreas: fluorescence was limited to the islets of Langherhans). The positivity in the ellipsoid region of the rods and cones of the eye and the absorption on different liver organelles showed that this aspect corresponded to the mitochondria. We propose to name this pattern 'antimitochondria antibody number 6' or 'anti-M6'. High titres of anti-M6 were found in four patients suffering from iproniazid-induced hepatitis. A decrease in the titre was obtained after stopping the treatment. The now exceptional use of iproniazid and the rare occurrence of anti-M6 suggest a link between these two phenomena. [ABSTRACT FROM AUTHOR]

Twenty sera from patients with systemic lupus erythematosus (SLE) and high titre of IgG anti-cardiolipin antibodies (ACA) were studied in order to evaluate the prevalence of anti- mitochondrial type 5 antibodies (AMA 5). None of these sera were found to be AMA 5 positive but five of 18 were positive for VDRL. Twenty sera from patients with AMA 5 were studied in order to evaluate the prevalence of ACA: only six of 20 were positive for ACA. In contrast to this finding. 15 of the 20 sera positive for AMA 5 were also positive for VDRL (P<0.001). The six sera positive for ACA and AMA 5 were absorbed with cardiolipin micelles. This absorption eliminated the ACA activity but not the AMA 5 activity. Despite the clinical similarities between the two groups of patients with AMA 5 or ACA. these data suggest that patients with AMA 5 and patients with ACA belong to two different subsets of SLE or SLE-like syndromes and that AMA 5 antigen is different from cardiolipin. [ABSTRACT FROM AUTHOR]

About 0.1% of the sera in human pathology produce a peculiar, cytoplasmic, non-organ- and non-species-specific fluorescence. This may easily be differentiated from the already described anti-organelle antibodies and, more particularly, from the mitochondrial antibodies of primary biliary cirrhosis. Should rat tissues he used in the immunofluorescence test, fluorescence predominates over the first two portions of the renal proximal tubules (P1 and P2) and the mucous neck cells of the stomach. This pattern may be attributed to mitochondria, and in particular to their inner membranes by fluorescent staining of the ellipsoid region of the rods and cones of the eyes, and by absorption with purified organelles. To distinguish this antibody from the already described mitochondrial antibodies, this one will be called mitochondrial antibody number 5 (M5). The seven carriers of this antibody suffer from systemic lupus erythematosus or autoimmune haemolytic anaemia. In these cases no diseases of the liver were observed, contrary to other classical mitochondrial antibodies. [ABSTRACT FROM AUTHOR]

Background/aims: Auto-immune hepatitis patients are divided into two well-defined subgroups on the basis of immunoserological markers, i.e. anti-actin cable and/or anti-nuclear antibodies for the auto-immune hepatitis type 1, anti-liver/kidney microsome type 1 and/or anti-liver cytosol type 1 for the autoimmune hepatitis type 2. Controversial antibodies to a soluble liver antigen have been proposed as a diagnostic marker for the putative auto-immune hepatitis type 3. The aim was to investigate the implication of anti-soluble liver antigen antibodies in the diagnosis of auto-immune hepatitis and their ability to define auto-immune hepatitis type 3., Methods: Sera from 483 patients with hepatic and non-hepatic diseases, and 102 sera from blood donors were analyzed by an inhibition capture enzyme-linked immunosorbent assay., Results: Anti-soluble liver antigen antibodies were found in 13 of the 106 (12%) auto-immune hepatitis type 1 patients and 10 of the 49 (20%) cryptogenic hepatitis patients tested. In contrast, they were not detected in auto-immune hepatitis type 2 (n=54), primary sclerosing cholangitis (n=37), primary biliary cirrhosis (n=52), hepatitis C virus infection (n=105), alcoholic hepatitis (n=25), various non-hepatic autoimmune disorders (n=55) and in healthy blood donors (n=102). The clinical and biological features of antisoluble liver antigen-seropositive patients were similar to those of auto-immune hepatitis type 1 and did not distinguish a subgroup of auto-immune hepatitis., Conclusion: The data support the concept that antisoluble liver antigen-positive cryptogenic hepatitis is similar to auto-immune hepatitis type 1. Anti-soluble liver antigen antibodies can be considered as an additional and specific auto-immune hepatitis type 1 diagnostic marker.

AUTOANTIBODY PRODUCTION: The production of autoantibodies can only occur if immune tolerance is circumvented. Thus drug-induced autoimmune hemolytic anemia requires that the drug have an effect on both autoantigens and on the immune system. AN EXAMPLE, METHYLDOPA: Methyldopa is a hypotensive agent which induces major production of anti-Rh IgG anti-erythrocyte autoantibodies, anti-nuclear antibodies and anti-actin antibodies. These autoantibodies generally appear 6 months after treatment onset and are observed in 20% of treated patients. Hemolysis is however exceptional and is only clinically or biologically perceptible in 1 to 2% of the patients who become immunized. Induced lupus has been reported as have been several dozen cases of drug-induced hepatitis with anti-actin autoantibodies. DRUGS INDUCING HEMOLYTIC ANEMIA: Besides methyldopa, other drugs known to induce hemolytic anemia include levodopa used for Parkinson's disease, mefenamic acid, a nonsteroidal antiinflammatory drug, interferon-alpha, used in chronic viral hepatitis, cyclosporin used for the prevention of graft rejection and the treatment of certain autoimmune diseases, and fludarabin, used in chronic lymphoid leukemia., Therapeutic Strategy: If there is no clinical or biological expression, the drug can be continued, excepting fludarabin where regular controls are needed. If hemolytic anemia is patent, the drug must be discontinued, transfusion and corticosteroid therapy should be envisaged.

Background & Aims: Anti-liver cytosol type 1 autoantibodies have been reported in association with anti-liver-kidney microsome type 1 autoantibodies in 30% of patients with autoimmune hepatitis type II. In 10% of cases, anti-liver cytosol type 1 antibodies are the only liver-related circulating autoantibodies. The liver cytosol antigen is a liver-specific 62-kilodalton protein present in the cell as an oligomer of approximately 240 kilodaltons. The aim of this study was to identify the antigen recognized by anti-liver cytosol antibody., Methods: To identify the liver cytosol antigen, an anti-liver cytosol type 1-positive serum was used for the screening of a complementary DNA library from HepG2 cells. Double immunodiffusion method was used to show the identity between the cytosolic and the cloned protein., Results: The sequence of two isolated clones showed 85.2% homology with the formiminotransferase cyclodeaminase (FTCD) enzyme from pig liver. Antibodies purified by affinity with the recombinant protein and sera from mice immunized with FTCD recognized a 62-kilodalton human cytosolic protein when tested by immunoblot. The identity of precipitation lines was found between the cytosolic antigen and FTCD., Conclusions: This enzyme is a liver-specific antigen recognized by the sera of patients with autoimmune hepatitis.

Although autoantibodies have been found in the serum of patients with chronic hepatitis C virus (HCV) there has been no convincing evidence of the presence of antimitochondrial antibodies, until now. Sera from 460 untreated patients with chronic hepatitis C were tested for antimitochondrial antibodies, using an indirect immunofluorescence technique; and if they tested positive for the antibodies (titer more than 1:50), they also were treated by Western blot analysis. Seven (1.5%) sera were positive. None of the patients had biological or histological evidence of primary biliary cirrhosis. Antimitochondrial antibodies recognized one of the oxo-dehydrogenase multienzyme complexe's epitopes by Western blot assay in three patients only. All seven patients were then treated by interferon alpha for six months. None showed exacerbation of liver disease during treatment. HCV-RNA disappeared from the serum in one patient who became negative for anti-M2 antibodies. The four patients who did not respond to interferon-alpha therapy, and the two who relapsed after treatment withdrawal, had sustained positive antimitochondrial antibodies. These data suggest that: 1) antimitochondrial antibodies present in patients with chronic hepatitis C do not always recognize the same epitopes as in primary biliary cirrhosis; 2) these antibodies may disappear after eradication of HCV, suggesting that the production of antimitochondrial antibodies is linked to the presence of the virus and 3) the clinical and biological course of chronic hepatitis C, and the response to interferon-alpha therapy, does not seem to be different in patients who are positive for antimitochondrial antibodies.

Between 10% and 42% of patients with primary biliary cirrhosis (PBC) have been reported to have autoantibodies directed against a restricted epitope of gp210, a glycoprotein of the nuclear pore membrane. The prevalence and specificity of these antibodies was studied in a French series of 285 patients with PBC and 497 control individuals affected with other liver or autoimmune diseases. Sera were analyzed by an enzyme-linked immunosorbent assay (ELISA) that used a synthetic polypeptide containing the predominant autoepitope of gp210, in parallel to immunoblotting of gp210 protein and immunofluorescence microscopy. Autoantibodies to the gp210 epitope detected by ELISA were 25.5% sensitive and 99.5% specific for the diagnosis of PBC. These results were in agreement with a 99.4% specificity with immunoblotting analysis and a 96.6% specificity with immunofluorescence. In a subset of PBC patients without detectable antimitochondrial autoantibodies (AMA), gp210 autoantibodies were found in 7 of 15 patients (47%). Therefore, gp210 autoantibodies are highly specific for PBC and may be of particular utility in assessing patients without AMA or with other atypical presentations.