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J C Homberg

Publications and source records attributed to J C Homberg.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Anti-mitochondrial antibodies type 5 are markers of antiphospholipid syndrome].

In order to investigate the clinical value of anti-mitochondrial antibodies type 5 (anti-M5), we carried out a retrospective study on 48 patients with these antibodies. Seventeen of these 48 patients (35%) satisfied at least 4 criteria of the revised American Rheumatism Association classification of SLE. Twenty-nine (61%) had at least one clinical manifestation of anti-phospholipid syndrome; thirteen had symptoms consistent with primary anti-phospholipid syndrome; five had isolated recurrent thrombosis; five had Evans' syndrome; four had auto-immune haemolytic anaemia; two had immunologic thrombocytopenia. Two of the 48 patients had no clinical manifestations, but only anti-M5 and a false laboratory test for syphilis (FBTS). Our data confirm that patients with anti-M5 have a high prevalence of: 1) thrombosis (42% had three or more deep thromboses) and fetal loss (21%); 2) auto-immune cytopenia with idiopathic thrombocytopenic purpura (29%) and auto-immune haemolytic anaemia (54%); 3) laboratory markers of anti-phospholipid syndrome (lupus anticoagulant (71%), FBTS (95%) and anticardiolipin antibodies (aCL) (71%). For 32 patients with anti-M5, anti-beta 2 glycoprotein I antibodies were also tested; 12 (38%) were positive, all of whom had IgG aCL, ie none had anti-beta 2GPI antibodies without aCL. There was no association between the presence of anti-beta 2GPI antibodies and recurrent thrombosis among patients with anti-M5. All these findings suggest that anti-M5 is another marker of the antiphospholipid syndrome. Even though the prevalence of anti-M5 is low, especially in SLE, it was the only marker of the anti-phospholipid syndrome in two patients; this appears to justify routine screening for these antibodies.

Adolescent↗
PubMed1994

[Prevalence and significance of non-specific anti-organelle antibodies of the liver in chronic viral hepatitis C].

OBJECTIVES: The aim of this study was to evaluate the prevalence and the clinical signification of non organ specific autoantibodies in chronic hepatitis C. METHODS: We studied retrospectively 158 consecutive patients (97 with chronic hepatitis C, 24 with chronic hepatitis B, 67 with alcoholic cirrhosis) and 100 blood-donors. RESULTS: The prevalence of anti-nuclear and anti-smooth muscle antibodies was lower in blood donors than in patients (P < 0.001), but was comparable among the 3 groups of patients. The anti-liver-kidney microsome type 1 antibodies were detected only in patients with chronic hepatitis C (6%). The serum gammaglobulin level was significantly higher in patients with hepatitis C and anti-nuclear antibody titers > or = 1/50. The anti-smooth muscle antibodies detected in patients with hepatitis C had no anti-actin specificity. The response to interferon was not related to the detection of non organ specific autoantibodies before treatment. CONCLUSION: Anti-nuclear or anti-smooth muscle antibodies are not characteristic of hepatitis C virus infection.

Adult↗
PubMed1994

[Prevalence and characteristics of anti-tissue antibodies in chronic hepatitis caused by hepatitis C virus].

OBJECTIVES: The prevalence and significance of antiorganelle antibodies in the serum of patients with chronic hepatitis C is a subject of controversy. We studied prospectively these characteristics in patients with chronic hepatitis C. METHODS AND RESULTS: Among 156 patients (age: 55 +/- 14 years; 83 females), 30 (19%) had significant titers of antiorganelle antibodies: anti-nuclear antibodies in 18, anti-smooth muscle antibodies in 8 (no anti-actin or anti-vimentine subtypes), anti-LKM1 in 2, type 2 anti-mitochondrial antibodies in 2 patients. Anti-organelle antibodies were not detected in 126 patients. Patients with anti-organelle antibodies were significantly older but no difference was found between the two groups for sex ratio, serum amino-transferases or gammaglobulins, histopathological liver activity or prevalence of lymphocytic sialadenitis. The presence of anti-organelle antibodies was not related to HLA phenotype, especially B8 DR3, or DR4. Response to alpha interferon, estimated by serum aminotransferase levels after six months of treatment, was the same in both groups. CONCLUSIONS: These results suggest that serum anti-organelle antibodies are prevalent in during chronic hepatitis C but do not indicate a distinct autoimmune mechanism. Furthermore, the typing of anti-smooth muscle antibodies might help distinguish chronic hepatitis C from type 1 autoimmune chronic hepatitis.

Adult↗
PubMed1993

Characterization of anti-liver-kidney microsome antibody (anti-LKM1) from hepatitis C virus-positive and -negative sera.

BACKGROUND: Hepatitis C virus-related antibodies were found in sera positive for antibodies to liver/kidney microsome antibody, usually considered a marker of autoimmune hepatitis. The aim of this study was to analyze the specificity of this autoantibody in sera from patients with and without hepatitis C virus infection. METHODS: Fifteen anti-hepatitis C virus- and anti-liver kidney microsome-positive sera were compared with 11 sera from patients with autoimmune hepatitis, for reactivity against rat and human liver microsomal proteins, P450IID6 recombinant proteins, and various synthetic peptides spanning the 241-429 amino acids sequence of the P450IID6. RESULTS: Ten of 11 sera from patients with autoimmune hepatitis bound to recombinant proteins spanning the P450IID6 region between amino acids 72 and 458. These sera bound to the 254-271 peptide, and some also recognized the 321-351, 373-389 and 410-429 peptides. Four of 15 antihepatitis C virus recognized the fusion protein coded by the full-length P450IID6 complementary DNA; 3 of them also reacted with the P450IID6 region between amino acids 72-456. Only 1 sera recognized the 321-351 peptide. CONCLUSIONS: P450IID6 antigenic sites recognized by anti-hepatitis C virus-positive sera were different from those recognized by sera from patients with autoimmune hepatitis.

Adolescent↗
PubMed1993

Non-organ specific autoantibodies associated with chronic C virus hepatitis.

Recently antibodies to hepatitis C virus were detected in sera of chronic active hepatitis patients, with anti-smooth muscle autoantibodies or with anti-liver/kidney microsomal type 1 autoantibodies. As the latter were used to differentiate autoimmune chronic active hepatitis from chronic non-A, non-B virus hepatitis, it was mainly important to discover if autoantibodies were associated with chronic hepatitis C virus infection. The sera of 272 chronic hepatitis C patients were screened by indirect immunofluorescence for non-organ specific autoantibodies. Antinuclear antibodies and anti-smooth muscle autoantibodies were more frequent in chronic hepatitis C patients than in blood donors (n = 100). Anti-liver/kidney microsomal type 1 autoantibodies were not detected in the sera of the blood donors, in the 74 hepatitis B patients or in the 30 alcoholic hepatitis or cirrhotic patients' sera tested as controls. They were detected in 14 chronic hepatitis C patients. These antibodies were compared in immunodiffusion to anti-liver/kidney microsomal type 1 autoantibodies sera obtained from type-2 autoimmune chronic active hepatitis patients and an identity reaction was observed. Chronic hepatitis C patients without or with anti-liver/kidney microsomal type 1 autoantibodies, did not differ in age, sex ratio, transaminases and gammaglobulin level, risk factors for hepatitis C virus infection, association with other autoimmune diseases. These patients differed significantly from type-2 autoimmune chronic active hepatitis patients. We conclude that: (i) in some chronic hepatitis C patients the pattern and the titer of autoantibodies may create confusion with an autoimmune chronic active hepatitis; (ii) There is no serological evidence for a hepatitis C virus infection in true type-2 autoimmune chronic active hepatitis.

Adolescent↗
PubMed1993

Autoimmune hepatitis associated with anti-actin antibodies in children and adolescents.

The clinical, biochemical, morphological, and evolutive features of autoimmune hepatitis associated with serum smooth muscle antibodies of anti-actin specificity were retrospectively analyzed in 31 children and adolescents. Cirrhosis was present at diagnosis in all but six patients, including nine of the 12 diagnosed within 6 months from the onset. In 15 children, one or more associated diseases of an immune-mediated mechanism were present, including chronic arthritis, sclerosing cholangitis, inflammatory bowel disease, and cutaneous vasculitis. All patients were treated with prednisone and azathioprine with normalization or improvement of liver function tests: 28 children are currently alive after a mean follow-up of 4 years, 10 months. Treatment was interrupted in four patients only. Two patients died of liver failure in spite of immunosuppressive therapy before the era of liver transplantation. In spite of prolonged therapy, five other patients ultimately required liver transplantation during adolescence or early adulthood. These results (a) further define a group of autoimmune hepatitis in children characterized by the presence of serum anti-actin antibodies; (b) indicate that immunosuppressive therapy improves liver function, although in most cases it must be continued for a long period to maintain remission; and (c) suggest that progressive liver failure may occur in early adulthood and may require liver transplantation.

Actins↗
PubMed1992

Characterization of the liver cytosol antigen type 1 reacting with autoantibodies in chronic active hepatitis.

An autoantibody to liver cytosol was previously described in childhood autoimmune chronic active hepatitis type 2. The antigen, liver cytosol antigen type 1, was for the first time partially purified using gel filtration and ion exchange chromatography, and it was characterized using immunodiffusion, immunoblot and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the immunoprecipitate. Immunoblot detected a unique antigenic peptide at 62 kD from human cytosol and at 58 kD from rat cytosol. The same peptides were also detected when immunoprecipitates of liver cytosol antigen type 1 and autoantibodies to liver cytosol antigen were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A polymeric structure, probably a tetramer, is suggested for native liver cytosol antigen type 1 because in gel filtration chromatography liver cytosol antigen type 1 was eluted as a protein of a molecular weight between 240 and 290 kD when human liver cytosol was fractionated and between 220 and 270 kD from rat liver cytosol. Liver cytosol antigen type 1 is probably poor in carbohydrates because it was not stained by periodic acid-Schiff stain. The autoantibodies to liver cytosol were frequently found in association with antiliver kidney microsomal autoantibodies type 1, which are directed against the cytochrome P-450 of the IID6 subfamily. Antiliver kidney microsomal autoantibodies type 1 but not antiliver cytosol autoantibodies were found in association with antibodies to hepatitis C virus. Autoantibodies to liver cytosol antigen type 1 seem to be a more specific marker for autoimmune hepatitis type 2 than antiliver kidney microsomal antibodies type 1 autoantibodies.

Animals↗
PubMed1991

Detection of human hepatitis anti-liver kidney microsomes (LKM2) autoantibodies on rat liver sections is predominantly due to reactivity with rat liver P-450 IIC11.

Anti-liver kidney microsomes (anti-LKM2) autoantibodies, appearing in patients treated with tienilic acid and suffering from hepatitis, react with proteins in rat liver sections. The nature of the rat proteins responsible for this recognition and detection of anti-LKM2 has been investigated. Immunoblot testing of the anti-LKM2 with liver microsomes from diversely treated rats and with purified rat liver cytochromes P450 (IA1, IA2, IIB1, IIB2, IIC6, IIC11 and IVA1) showed that these antibodies cross-reacted with cytochrome P450IIC11 and also with phenobarbital-induced cytochromes P450IIB1 and IIB2. Moreover, metabolic activation of tienilic acid and of a tienilic acid isomer by untreated rat liver microsomes was partially inhibited by anti-LKM2. On the other hand, monospecific polyclonal anti-rat P450IIC11 antibodies cross-reacted with human microsomal cytochromes P450 and recognized the same cytochromes P450 as anti-LKM2. This antibody also gave an immunofluorescence pattern on rat and mouse liver and kidney sections very similar to anti-LKM2. The data presented here show that anti-LKM2 recognize epitopes shared by rat P450 IIC11, and a human P450 of the family IIC. All the results indicate rat P450 IIC11, the major isoenzyme present in normal adult male rat liver, as the main antigen recognized by human anti-LKM2 autoantibodies; this is the basis of the immunofluorescence test for detection of these antibodies.

Animals↗
PubMed1990

Detection of autoantibodies to Sm antigen in systemic lupus erythematosus by immunodiffusion, ELISA and immunoblotting: variability of incidence related to assays and ethnic origin of patients.

Autoantibodies to small nuclear ribonucleoproteins (snRNP) were studied using the techniques of immunodiffusion, ELISA, and immunoblotting in the sera of 150 patients with systemic lupus erythematosus (SLE), and of 29 patients with mixed connective tissue disease; 900 control patients and 100 normal blood donors were examined simultaneously. The incidence of anti-Sm antibodies in French SLE patients was low compared with the occurrence observed in similar studies in USA (even when highly sensitive assays were used) but was of the same magnitude as European results. Frequency of anti-Sm antibodies in SLE patients varied moderately when detected by immunodiffusion (12%), or by immunoblotting (17%), however, it seems that the ethnic and/or genetic background of patients induces more significant differences. SLE patients from the French West Indies had anti-Sm antibodies in 39% of cases when detected by immunodiffusion and in 50% when immunoblotting was used. In these patients the incidence of the antibodies was five times more frequent than that of mainland French patients. Immunization against snRNP does not seem to be a common feature of all SLE patients.

Antibody Specificity↗
PubMed1990

[Anti-Scl-70 antibodies in systemic scleroderma].

We looked for anti-Scl-70 and anti-centromere antibodies in 109 patients (26 men and 83 women). Mean age was 43 +/- 15 years. Forty patients had systemic sclerosis according to ARA criteria. The extension of cutaneous involvement was defined by using Barnett and Coventry criteria: 12 patients were type I (sclerodactyly), 20 type II (acrosclerosis) and 8 type III (diffuse scleroderma). Among the 12 patients with type I, there were 8 cases of CREST syndrome defined as follows: presence of sclerodactyly, Raynaud's phenomenon and 2 of the 3 following criteria: oesophageal dysmotility, calcinosis, telangiectasia. Other organ involvement was recorded. Control patients had idiopathic Raynaud's phenomenon (n = 22), other connective tissue diseases (n = 20), and miscellaneous diseases (n = 28). Ninety-nine patients were prospectively included in this study. Patients' sera were stored at -20 degrees C. Ten previously stored sera obtained from patients with systemic sclerosis were also analyzed. Immunological tests were performed simultaneously and with no information on the diagnosis. When antinuclear antibodies were detected by indirect immunofluorescence, double immunodiffusion and immunoblotting were performed. Anti-Scl-70 antibodies were detected in systemic sclerosis only: 1 of 12 type I, 11 of 20 type II and 4 of 8 type III. One serum negative by immunodiffusion was positive using immunoblotting. We found that the specificity of anti-Scl-70 antibodies for systemic sclerosis was 100 p. 100 and their sensitivity 40 p. 100. There was a correlation between the presence of anti-Scl-70 antibodies and the presence of antinuclear antibodies (p less than 0.05) and the extent of cutaneous involvement (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

A human cytochrome P-450 is recognized by anti-liver/kidney microsome antibodies in autoimmune chronic hepatitis.

1- Anti-liver/kidney microsome autoantibodies type 1 (anti-LKM1), observed in some children with chronic active hepatitis, were used to isolate their antigen in human liver microsomes. A protein, called P-LKM1 was thus purified. This protein was recognized by a rabbit antiserum directed against the related human cytochromes P-450 bufI and P-450 bufII. 2- A human liver microsomal protein immunoprecipitated with anti-LKM1 sera was also recognized by anti cytochromes P-450 bufI/II antibodies. 3- Anti-LKM1 antibodies potently inhibited microsomal bufuralol 1'-hydroxylation. These results displayed the possible identity between cytochrome P-450 bufI/II and LKM1 antigen.

Autoantibodies↗
PubMed1989

Characteristics of clometacin-induced hepatitis with special reference to the presence of anti-actin cable antibodies.

The clinical, biochemical, histopathological and immunological features of 30 cases of clometacin-induced hepatitis are described. The age range of the patients was 32-84 years with a notable female predominance of 29:1. The hepatitis was highly cytolytic with high values of transaminases but with little or no cholestasis. Gammaglobulins were higher than 18 g/l in 73% of the cases. 25 liver biopsies were performed and showed acute hepatitis with a predominant centrilobular necrosis in 17; chronic aggressive hepatitis was noted in 8 cases but 1 showed concomitant cirrhotic changes. Anti-tissue antibodies were looked for in all cases. Anti-smooth muscle antibodies of anti-actin cable type (titre 1/80 to 1/2, 560) were detected in 19 cases, anti-nucleus antibodies in 16 cases which were associated to the former in 14 cases. The above findings show that clometacin produces a hepatitis syndrome quite akin to autoimmune chronic active hepatitis (lupoid hepatitis) and to the hepatopathy induced by oxyphenisatin.

Actins↗
PubMed1988

Organ-specific autoantibodies in HLA genotyped insulin-dependent diabetes mellitus families.

The prevalence of cytoplasmic islet cell antibodies (ICA) and extrapancreatic antibodies (EPA), (stomach, adrenal and thyroid) was investigated in 132 juvenile onset diabetic patients, without personal or familial history of other autoimmune disease, and their 31 diabetic and 402 non-diabetic first degree relatives. The prevalence of ICA was 59% in index cases and 12% in the non-affected first degree relatives. The frequency of EPA was 23% and 16% respectively. There were no sex-related differences among the patients. However, among the non-affected relatives, an increased frequency of EPA was observed in females (23%) compared to males (8%) (P less than 10-4). There was a higher prevalence of ICA in healthy relatives bearing DR3 and/or DR4 antigen combinations compared to non-DR3 and non-DR4 individuals (14% versus 5%, P less than 0.05). Furthermore, ICA were more frequent in healthy siblings sharing two haplotypes compared with one or no haplotype (21% vs 10%, P less than 0.05). These results support the heterogeneity of the autoantibodies: ICA are related closely to diabetes, decline in frequency with the duration of the disease and show association with DR3 or DR4 and the number of HLA haplotypes shared with the proband; EPA are sex related, independent of the duration of diabetes, non-HLA linked, and clustered in families with parent-offspring overtransmission, reflecting an overlapping autoimmune background.

Adolescent↗
PubMed1988

Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems with different selectivity for the two cytochrome P-450 isozymes catalyzing bufuralol metabolism in human liver, we show that anti-LKM1 exclusively recognizes cytochrome P-450db1. Immunopurification of the LKM1 antigen from solubilized human liver microsomes resulted in an electrophoretically homogenous protein that had the same molecular mass (50 kDa) as purified P-450db1 and an identical N-terminal amino acid sequence. Recognition of both purified P-450db1 and the immunoisolated protein on western blots by several monoclonal antibodies confirmed the identity of the LKM1 antigen with cytochrome P-450db1. Cytochrome P-450db1 has been identified as the target of a common genetic polymorphism of drug oxidation. However, the relationship between the polymorphic cytochrome P-450db1 and the appearance of anti-LKM1 autoantibodies as well as their role in the pathogenesis of chronic active hepatitis remains speculative.

Antibodies, Monoclonal↗
PubMed1987

Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug.

"Anti-liver/kidney microsome" (anti-LKM) autoantibodies have been found in the serum of patients with cryptogenic chronic hepatitis and with immunoallergic drug-induced hepatitis, such as those induced by halothane or by tienilic acid (called anti-LKM2 in this case). So far the nature of the human microsomal macromolecules recognized by these antibodies has not been determined. Here we show, by using immunoblot techniques, that among the macromolecules present in human adult liver microsomes, one protein called cytochrome P-450-8 is specifically recognized by most sera of patients containing anti-LKM2 antibodies but not by control serum. Human fetal liver microsomes that do not contain cytochrome P-450-8 are not recognized by the anti-LKM2 antibodies. It is also shown that anti-cytochrome P-450-8 antibodies as well as human serum containing anti-LKM2 antibodies specifically inhibit the hydroxylation of tienilic acid by human liver microsomes. These results indicate that anti-LKM2 antibodies appearing in patients with hepatitis and concomitant administration of tienilic acid are directed against a cytochrome P-450 isoenzyme that catalyzes the metabolic oxidation of this drug. This suggests a possible mechanism for the appearance of anti-organelle antibodies in a drug-induced hepatitis.

Adult↗