The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Fernando Alvarez - One of the best experts on this subject based on the ideXlab platform.
-
Brief Definitive Report ANTI-LIVER Kidney Microsome ANTIBODY RECOGNIZES A CYTOCHROME P450 FROM THE III) SUBFAMILY
2013Co-Authors: Maryse Gueguen, Olivier Bernard, Michele Meunierrotival, Fernando AlvarezAbstract:Children with autoimmune chronic active hepatitis can be separated into two groups depending on the presence in their serum of either anti-smooth muscle antibody (SMA) or anti-liver-Kidney Microsome antibody (LKMA) (1). LKMA-positive autoimmune chronic active hepatitis may be detected early in life, present different clinical patterns, and is frequently associated with extrahepatic autoimmune manifestations (2). The antigen recognized by LKMA has been identified as a protein with an,M, of 50 kD, present in a higher concentration in smooth than in rough Microsomes. This 50-kD protein is an integral membrane protein exposed on the cytoplasmic side of the microsomal membrane (3). These properties are typical of the cytochromes, a family of hemeprotein monooxygenase isozymes present in large amounts in hepatocytes. It was recently shown that LKMA crossreacts with two methylcholantrene-inducible isozymes ofcytochrome P450 on dot-blot analysis, suggesting that the antigene, present in noninduced Microsomes, has some common epitopes with these P450 isozymes and could be a constitutive form of cytochrome P450 (4). Here, we show that LKMA recognizes cytochrome P450 forms from th
-
Brief Definitive Report ANTI-LIVER-Kidney Microsome ANTIBODY RECOGNIZES A 50,000 MOLECULAR WEIGHT PROTEIN OF THE ENDOPLASMIC RETICULUM
2013Co-Authors: Fernando Alvarez, Jean-claude Homberg, Olivier Bernard, Gert KreibichAbstract:Children with autoimmune chronic active hepatitis can be separated into two groups depending on the presence in the serum of either smooth muscle antibody (SMA) or liver-Kidney Microsome antibody (LKMA) (1). The latter can be detected by immunofluorescence as a cytoplasmic staining of hepatocytes and of Kidney tubular cells in sections from the respective rat organs (2). Indeed, it has been shown by immunoelectron microscopy that LKMA binds to constitutents of the endoplasmic reticulum of rat hepatocytes (3). Using recent developments in cell fractionation and immunological techniques, we have determined that the antigen recognized by LKMA is an integral membrane protein of 50,000 mol wt located primarily in the smooth endoplasmic reticulum. Materials and Methods Sera. LKMA-positive sera were obtained from five children with chronic active hepatitis as proven by liver biopsy (immunofluorescence LKMA titer, 1:500 to 1:100,000; serum gamma globulin levels, 13.5-43 g/i). As a control we studied the sera from 20 children with various chronic inflammatory liver diseases whose sera were negative fo
-
Anti-soluble liver antigen/liver-pancreas (SLA/LP) antibodies in pediatric patients with autoimmune hepatitis.
Autoimmunity, 2002Co-Authors: Susana Vitozzi, Pascal Lapierre, Idriss Djilali-saiah, Fernando AlvarezAbstract:Antibodies against soluble liver antigen/liver-pancreas (SLA/LP) have been associated with severe autoimmune hepatitis (AIH) and poor outcome, but most of these reports have focused on adult patients. The aim of this study was to assess the prevalence and clinical significance of anti-SLA/LP antibodies in a pediatric population with AIH. We developed a quantitative enzyme-linked immunoassay (ELISA), a Western blot (WB) and an immunoprecipitation assay (IPA) based on recombinant cDNA from activated Jurkat cells. The specificity of these tests was validated by testing 200 serum samples from healthy subjects, and from patients with liver and non-liver diseases. Anti-SLA/LP antibodies were found in patients with type 1 and type 2 AIH. The prevalence of these antibodies in patients with type 1 AIH was: 42% when tested by ELISA, 15% by WB and 50% by IPA. In patients with type 2 AIH, the prevalence rates were 42% by ELISA, 18% by WB and 44% by IPA. The mean titer values for anti-SLA/LP antibodies was significantly higher in type 2 AIH (1:1,300 +/- 339) than in type 1 AIH (1:600 +/- 71; p < 0.0001) and closely associated with higher titers of anti-liver Kidney Microsome type 1 (LKM1) and anti-liver cytosol type 1 (LC1) antibodies in sera. The presence of anti-SLA/LP showed a significant female preponderance in type 1 and 2 AIH patients (p = 0.0003 and p = 0.003, respectively), and was significantly correlated with a lower age at diagnosis (p = 0.05) in type 1 AIH patients. In conclusion, anti-SLA/LP antibodies in pediatric patients are associated with both type 1 and 2 AIH.
-
Sera of children with hepatitis C infection and anti-liver-Kidney Microsome-1 antibodies recognize different CYP2D6 epitopes than adults with LKM+/HCV+ sera.
Journal of pediatric gastroenterology and nutrition, 1999Co-Authors: Denise Herzog, Ana Maria Yamamoto, Giuseppe Maggiore, Paloma Jara, Jacques Sarles, Fernando AlvarezAbstract:Background: Liver-Kidney Microsome type I (LKMI) antibodies are specific markers of autoimmune hepatitis (AIH) type 2. Antibodies to LKM 1 have been found in 2% to 3% of adults infected with hepatitis C virus (HCV) without AIH. Thirty percent of these antibodies are directed against linear sequences of CYP2D6 protein. LKM1 antibodies in HCV+/LKM1+ sera and in sera of AIH patients do not recognize the same CYP2D6 epitopes. The current study was conducted to determine whether LKM antibodies in HCV+/LKM1+ children's sera are the result of the same immune response as the antibodies described in AIH type 2 and in HCV+/LKM1+ adult patients. Methods: Sera from 10 HCV+/LKM1+ children were tested against human liver microsomal and cytosolic proteins by Western blot analysis and against synthetic peptides of the CYP2D6 sequence between amino acids 200 and 429 by dot blot. The same sera were tested against radiolabeled CYP2D6 by immunoprecipitation. Results: Four of 10 sera tested by Western blot analysis showed immunoglobulin (Ig) G-type antibodies against CYP2D6, and 2 had antibodies against proteins of 58, 66, and 84 kDa. One of the sera also contained IgM-type anti-66-kDa and 84-kDa proteins. The radioligand test detected anti-CYP2D6 antibodies in 9 of 10 patients. Five of the anti-CYP2D6-positive sera recognized a peptide between amino acids 200 and 429 including amino acids 254-271. Conclusions: Most HCV+/LKM1+ sera from children recognize conformational epitopes of the CYP2D6 antigen, and half recognize linear epitopes. Some HCV+/LKM1+ sera demonstrated antibodies against the AIH type 2 main antigenic site of the CYP2D6. Screening of HCV RNA should be performed before starting treatment of presumed autoimmune hepatitis associated with LKM 1.
-
Characterization of anti-liver-Kidney Microsome antibody (anti-LKM1) from hepatitis C virus-positive and -negative sera.
Gastroenterology, 1993Co-Authors: Ana M. Yamamoto, Jean-claude Homberg, Danièle Cresteil, Fernando AlvarezAbstract:Abstract 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 anti-hepatitis 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.
Eric Ballot - One of the best experts on this subject based on the ideXlab platform.
-
Significance of antibodies to soluble liver antigen/liver pancreas: a large French study.
Liver international : official journal of the International Association for the Study of the Liver, 2009Co-Authors: Violaine Eyraud, Eric Ballot, Olivier Chazouillères, Christophe Corpechot, Raoul Poupon, Catherine JohanetAbstract:Background: Antibodies to soluble liver antigen (SLA)/liver pancreas (LP) are generally considered as highly specific diagnostic markers of type 1 auto-immune hepatitis (AIH-1), and are particularly useful in patients without conventional antibodies. However, the presence of anti-SLA/LP in type 2 auto-immune hepatitis (AIH-2), primary sclerosing cholangitis (PSC) and hepatitis C has recently been reported. The aim was thus to describe the characteristics of anti-SLA/LP-positive patients in the largest series reported to date. Methods: Sera were selected from the period between 1998 and 2005, based on the presence of antibodies to SLA/LP detected by two methods. The clinical status of patients was determined from their medical records. Results: Eighty-one anti-SLA/LP-positive patients with available clinical data were included: 89% (72/81) had a diagnosis of AIH-1, including 10 (12%) associated with cholestatic diseases (primary biliary cirrhosis in seven cases and PSC in three cases). Six patients (7%) suffered from another liver disease: hepatitis C (n=3) and drug-induced hepatitis (n=3). No specific diagnosis was made in three patients. Conclusions: Antibodies to SLA/LP are of a major diagnostic value for AIH-1, including paediatric forms and overlap syndromes with cholestatic diseases, but are not found in association with anti-liver/Kidney/Microsome type 1 or antibodies to liver cytosol type 1. They are rarely present in other liver diseases such as hepatitis C and drug-induced hepatitis.
-
Identification by proteomic tool of atypical anti-liver/Kidney Microsome autoantibodies targets in de novo autoimmune hepatitis after liver transplantation.
Annals of the New York Academy of Sciences, 2007Co-Authors: S. Huguet, Catherine Johanet, Joëlle Vinh, Didier Samuel, Michele Gigou, Oana Zamfir, Jean-charles Duclos-vallée, Eric BallotAbstract:De novo autoimmune hepatitis (AIH) occurs after liver transplantation for nonautoimmune disorders. Autoantibodies so-called atypical anti-liver/Kidney Microsome antibodies (LKMA) with an unusual liver/Kidney cytoplasmic staining as judged by indirect immunofluorescence, can be detected in some patients' sera. Few studies investigated their molecular targets, and the aim of this work was to identify the atypical anti-LKMA targets by proteomic tool. This proteomic approach consisted of (a) two-dimensional gel electrophoresis of cytosolic and microsomal proteins obtained by differential centrifugations of rat liver and rat Kidney, followed by (b) two-dimensional immunoblotting with sera of patients with de novo AIH (n = 8, including 2 with anti-LKMA antibodies) and then (c) identifications of interest spots performed by ion trap mass spectrometry. By this way several proteins at 25 kDa were unambiguously identified: isoforms of carbonic anhydrase III, members of different glutathione S-transferase (GST) families, and subunit beta1 of proteasome. This is the first report of proteasome and carbonic anhydrase III as autoantigens in de novo AIH. These results could lead to a better diagnosis of this disease using identified autoantigens in diagnostic tests, and strengthen proteomic approach as a new way of autoantigens investigation.
-
identification by proteomic tool of atypical anti liver Kidney Microsome autoantibodies targets in de novo autoimmune hepatitis after liver transplantation
Annals of the New York Academy of Sciences, 2007Co-Authors: S. Huguet, Catherine Johanet, Joëlle Vinh, Didier Samuel, Michele Gigou, Oana Zamfir, Jeancharles Duclosvallee, Eric BallotAbstract:De novo autoimmune hepatitis (AIH) occurs after liver transplantation for nonautoimmune disorders. Autoantibodies so-called atypical anti-liver/Kidney Microsome antibodies (LKMA) with an unusual liver/Kidney cytoplasmic staining as judged by indirect immunofluorescence, can be detected in some patients' sera. Few studies investigated their molecular targets, and the aim of this work was to identify the atypical anti-LKMA targets by proteomic tool. This proteomic approach consisted of (a) two-dimensional gel electrophoresis of cytosolic and microsomal proteins obtained by differential centrifugations of rat liver and rat Kidney, followed by (b) two-dimensional immunoblotting with sera of patients with de novo AIH (n = 8, including 2 with anti-LKMA antibodies) and then (c) identifications of interest spots performed by ion trap mass spectrometry. By this way several proteins at 25 kDa were unambiguously identified: isoforms of carbonic anhydrase III, members of different glutathione S-transferase (GST) families, and subunit beta1 of proteasome. This is the first report of proteasome and carbonic anhydrase III as autoantigens in de novo AIH. These results could lead to a better diagnosis of this disease using identified autoantigens in diagnostic tests, and strengthen proteomic approach as a new way of autoantigens investigation.
-
Antibodies to soluble liver antigen: an additional marker in type 1 auto-immune hepatitis
Journal of hepatology, 2000Co-Authors: Eric Ballot, Catherine JohanetAbstract:Abstract 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 auto-immune disorders ( n =55) and in healthy blood donors ( n =102). The clinical and biological features of anti-soluble 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 anti-soluble 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.
-
detection on immunoblot of new proteins from the soluble fraction of the cell recognized either by anti liver Kidney Microsome antibodies type 1 or by anti liver cytosol antibodies type 1 relationship with hepatitis c virus infection
Clinical Immunology and Immunopathology, 1996Co-Authors: Eric Ballot, A Desbos, J C MonierAbstract:Abstract Antibodies directed against liver cytosol protein, called anti-liver cytosol type 1 (LC1 Ab), have been described by both immunofluorescence (IF) and immunodiffusion techniques in sera from patients with autoimmune hepatitis (AIH). They have never been found in association with antibodies directed against the hepatitis C virus (HCV), unlike the anti-liver–Kidney Microsome antibodies type 1 (LKM1 Ab), the serological marker of AIH type 2. This suggests that there are two subgroups of AIH type 2, i.e., HCV-related and non-HCV-related. In this study, immunoblotting experiments were performed using proteins from the soluble phase of the rat liver cell; 141 sera which tested positive for LKM1 Ab by IF, 24 identified as having LC1 Ab by IF, and 50 from blood donors as controls were analyzed. Three bands were stained by LC1 Ab sera more often than by the control sera, and with a statistically significant frequency. These 3 proteins were located at apparentMr50,000, 55,000, and 60,000. The LKM1 Ab-positive sera as defined by IF stained six bands with a statistically significant frequency compared to the controls. Their apparentMrwere 35,000, 39,000, 47,000, 50,000, 55,000, and 60,000. LKM1 Ab-positive sera which were anti-HCV negative recognized a 60,000 protein belonging to the soluble phase of the cell, with a statistically significant frequency compared to LKM1 Ab-positive sera which were anti-HCV positive. This 60,000 protein was also recognized by LC1 Ab-positive sera, which were almost always anti-HCV negative. The presence of antibodies against a 60,000 protein from the soluble phase of the cell is discussed in terms of the anti-HCV serological markers found in the sera from patients with AIH.
Catherine Johanet - One of the best experts on this subject based on the ideXlab platform.
-
Significance of antibodies to soluble liver antigen/liver pancreas: a large French study.
Liver international : official journal of the International Association for the Study of the Liver, 2009Co-Authors: Violaine Eyraud, Eric Ballot, Olivier Chazouillères, Christophe Corpechot, Raoul Poupon, Catherine JohanetAbstract:Background: Antibodies to soluble liver antigen (SLA)/liver pancreas (LP) are generally considered as highly specific diagnostic markers of type 1 auto-immune hepatitis (AIH-1), and are particularly useful in patients without conventional antibodies. However, the presence of anti-SLA/LP in type 2 auto-immune hepatitis (AIH-2), primary sclerosing cholangitis (PSC) and hepatitis C has recently been reported. The aim was thus to describe the characteristics of anti-SLA/LP-positive patients in the largest series reported to date. Methods: Sera were selected from the period between 1998 and 2005, based on the presence of antibodies to SLA/LP detected by two methods. The clinical status of patients was determined from their medical records. Results: Eighty-one anti-SLA/LP-positive patients with available clinical data were included: 89% (72/81) had a diagnosis of AIH-1, including 10 (12%) associated with cholestatic diseases (primary biliary cirrhosis in seven cases and PSC in three cases). Six patients (7%) suffered from another liver disease: hepatitis C (n=3) and drug-induced hepatitis (n=3). No specific diagnosis was made in three patients. Conclusions: Antibodies to SLA/LP are of a major diagnostic value for AIH-1, including paediatric forms and overlap syndromes with cholestatic diseases, but are not found in association with anti-liver/Kidney/Microsome type 1 or antibodies to liver cytosol type 1. They are rarely present in other liver diseases such as hepatitis C and drug-induced hepatitis.
-
Identification by proteomic tool of atypical anti-liver/Kidney Microsome autoantibodies targets in de novo autoimmune hepatitis after liver transplantation.
Annals of the New York Academy of Sciences, 2007Co-Authors: S. Huguet, Catherine Johanet, Joëlle Vinh, Didier Samuel, Michele Gigou, Oana Zamfir, Jean-charles Duclos-vallée, Eric BallotAbstract:De novo autoimmune hepatitis (AIH) occurs after liver transplantation for nonautoimmune disorders. Autoantibodies so-called atypical anti-liver/Kidney Microsome antibodies (LKMA) with an unusual liver/Kidney cytoplasmic staining as judged by indirect immunofluorescence, can be detected in some patients' sera. Few studies investigated their molecular targets, and the aim of this work was to identify the atypical anti-LKMA targets by proteomic tool. This proteomic approach consisted of (a) two-dimensional gel electrophoresis of cytosolic and microsomal proteins obtained by differential centrifugations of rat liver and rat Kidney, followed by (b) two-dimensional immunoblotting with sera of patients with de novo AIH (n = 8, including 2 with anti-LKMA antibodies) and then (c) identifications of interest spots performed by ion trap mass spectrometry. By this way several proteins at 25 kDa were unambiguously identified: isoforms of carbonic anhydrase III, members of different glutathione S-transferase (GST) families, and subunit beta1 of proteasome. This is the first report of proteasome and carbonic anhydrase III as autoantigens in de novo AIH. These results could lead to a better diagnosis of this disease using identified autoantigens in diagnostic tests, and strengthen proteomic approach as a new way of autoantigens investigation.
-
identification by proteomic tool of atypical anti liver Kidney Microsome autoantibodies targets in de novo autoimmune hepatitis after liver transplantation
Annals of the New York Academy of Sciences, 2007Co-Authors: S. Huguet, Catherine Johanet, Joëlle Vinh, Didier Samuel, Michele Gigou, Oana Zamfir, Jeancharles Duclosvallee, Eric BallotAbstract:De novo autoimmune hepatitis (AIH) occurs after liver transplantation for nonautoimmune disorders. Autoantibodies so-called atypical anti-liver/Kidney Microsome antibodies (LKMA) with an unusual liver/Kidney cytoplasmic staining as judged by indirect immunofluorescence, can be detected in some patients' sera. Few studies investigated their molecular targets, and the aim of this work was to identify the atypical anti-LKMA targets by proteomic tool. This proteomic approach consisted of (a) two-dimensional gel electrophoresis of cytosolic and microsomal proteins obtained by differential centrifugations of rat liver and rat Kidney, followed by (b) two-dimensional immunoblotting with sera of patients with de novo AIH (n = 8, including 2 with anti-LKMA antibodies) and then (c) identifications of interest spots performed by ion trap mass spectrometry. By this way several proteins at 25 kDa were unambiguously identified: isoforms of carbonic anhydrase III, members of different glutathione S-transferase (GST) families, and subunit beta1 of proteasome. This is the first report of proteasome and carbonic anhydrase III as autoantigens in de novo AIH. These results could lead to a better diagnosis of this disease using identified autoantigens in diagnostic tests, and strengthen proteomic approach as a new way of autoantigens investigation.
-
Antibodies to soluble liver antigen: an additional marker in type 1 auto-immune hepatitis
Journal of hepatology, 2000Co-Authors: Eric Ballot, Catherine JohanetAbstract:Abstract 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 auto-immune disorders ( n =55) and in healthy blood donors ( n =102). The clinical and biological features of anti-soluble 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 anti-soluble 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.
Ryuzo Ueda - One of the best experts on this subject based on the ideXlab platform.
-
effect of interferon therapy on japanese chronic hepatitis c virus patients with anti liver Kidney Microsome autoantibody type 1
Journal of Gastroenterology and Hepatology, 2001Co-Authors: Yoshihiko Iijima, Hiroshi Miyakawa, Takanobu Kato, Masataka Ogino, Makoto Mizuno, Kanji Sugihara, Takahiro Ando, Kei Fujiwara, Etsuro Orito, Ryuzo UedaAbstract:Aim: The aim of this study was to determine the prevalence of anti-liver/Kidney Microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. Methods: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/Kidney Microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. Results: Anti-liver/Kidney Microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. Conclusion: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease.
-
Effect of interferon therapy on Japanese chronic hepatitis C virus patients with anti-liver/Kidney Microsome autoantibody type 1.
Journal of gastroenterology and hepatology, 2001Co-Authors: Yoshihiko Iijima, Hiroshi Miyakawa, Takanobu Kato, Masataka Ogino, Makoto Mizuno, Kanji Sugihara, Takahiro Ando, Kei Fujiwara, Etsuro Orito, Ryuzo UedaAbstract:Aim: The aim of this study was to determine the prevalence of anti-liver/Kidney Microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. Methods: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/Kidney Microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. Results: Anti-liver/Kidney Microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. Conclusion: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease.
Hiroshi Miyakawa - One of the best experts on this subject based on the ideXlab platform.
-
effect of interferon therapy on japanese chronic hepatitis c virus patients with anti liver Kidney Microsome autoantibody type 1
Journal of Gastroenterology and Hepatology, 2001Co-Authors: Yoshihiko Iijima, Hiroshi Miyakawa, Takanobu Kato, Masataka Ogino, Makoto Mizuno, Kanji Sugihara, Takahiro Ando, Kei Fujiwara, Etsuro Orito, Ryuzo UedaAbstract:Aim: The aim of this study was to determine the prevalence of anti-liver/Kidney Microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. Methods: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/Kidney Microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. Results: Anti-liver/Kidney Microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. Conclusion: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease.
-
Effect of interferon therapy on Japanese chronic hepatitis C virus patients with anti-liver/Kidney Microsome autoantibody type 1.
Journal of gastroenterology and hepatology, 2001Co-Authors: Yoshihiko Iijima, Hiroshi Miyakawa, Takanobu Kato, Masataka Ogino, Makoto Mizuno, Kanji Sugihara, Takahiro Ando, Kei Fujiwara, Etsuro Orito, Ryuzo UedaAbstract:Aim: The aim of this study was to determine the prevalence of anti-liver/Kidney Microsome autoantibody type 1 (anti-LKM-1) among hepatitis C virus (HCV)-infected Japanese patients at various stages (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma), and to assess the influence of anti-LKM-1 on interferon therapy. Methods: A total of 390 serum samples from 215 HCV-infected patients with chronic hepatitis (HCV-CH), 81 HCV-infected patients with liver cirrhosis (HCV-LC), and 94 HCV-HCC infected patients were subjected to examination. Ninety-one HBsAg-positive patients and 137 healthy subjects served as controls. Anti-liver/Kidney Microsome autoantibody type 1 was determined by using a newly developed ELISA using recombinant cytochrome P450 IID6 as the antigen. Results: Anti-liver/Kidney Microsome autoantibody type 1 was detected in six of the 390 (1.5%) chronic HCV-infected patients (four were HCV-CH and two were HCV-LC); in contrast, it was not detected in control groups. Among the 110 HCV-CH patients treated with interferon (IFN), four were positive for anti-LKM-1. No change in anti-LKM-1 immunoreactivity from negative to positive during interferon therapy was observed. Moreover, no increase in the serum alanine aminotransferase level was observed in these four patients with anti-LKM-1. Conclusion: Our study indicates that: (i) anti-LKM-1 does not aggravate the liver disease associated with HCV infection; and (ii) no change in anti-LKM-1 immunoreactivity from negative to positive or no aggravations of liver dysfunction were observed among HCV-CH patients during the IFN therapy for Japanese patients with liver disease.
-
Differences in antigenic sites, recognized by anti-liver-Kidney Microsome-1 (LKM-1) autoantibody, between HCV-positive and HCV-negative sera in Japanese patients.
Journal of gastroenterology, 1998Co-Authors: Hiroshi Miyakawa, Kazuhiro Abe, Eriko Kitazawa, Masanao Matsushita, Hirotoshi Fujikawa, Kentaro Kikuchi, Hiroshi Matsushima, Yoichi Narita, Raleigh W. Hankins, Naomi KawaguchiAbstract:Anti-liver-Kidney Microsome-1(LKM-1), which reacts with cytochrome P450 IID6 (CYP2D6), is an autoantibody present in autoimmune hepatitis type II, which affects primarily young patients. Recently, it has been shown some adult patients with chronic hepatitis C are also positive for anti-LKM-1. Thus, anti-LKM-1-positive patients can be classified into two subgroups: (1) those with autoimmune hepatitis type II and (2) those with chronic hepatitis C. We investigated the antigenic epitopes of CYP2D6 with which each of these two anti-LKM-1-positive subgroups reacted. Multiple deletion mutants of CYP2D6 were constructed from a human liver cDNA library and five recombinant fusion proteins expressed. Antigenic epitopes were determined by immunoblot analysis using these proteins. Anti-LKM-1 present in HCV-negative sera recognized at least two peptide regions of aa213-280 and aa341-477 of human CYP2D6. In contrast, anti-LKM-1 present in HCV-positive sera recognized only a single region of aa341-477. Thus, the sera of patients with autoimmune hepatitis type II and patients with chronic hepatitis C recognize different antigenic epitopes of the CYP2D6 molecule. To our knowledge, this is the first time LKM-1 autoantigens have been analyzed at the molecular level in Japanese patients.
-
Anti-liver-Kidney Microsome-1 autoantibody in HCV-positive sera reacts predominantly to conformational epitope, not to linear epitope
Hepatology Research, 1998Co-Authors: Hiroshi Miyakawa, Kazuhiro Abe, Eriko Kitazawa, Masanao Matsushita, Naomi Kawaguchi, Hirotoshi Fujikawa, Kentaro Kikuchi, Makoto KakoAbstract:Abstract Anti-liver/Kidney Microsome (LKM)-1 autoantibody, which is a marker of autoimmune hepatitis type II, recognizes cytochrome P450IID6 (CYP2D6). Four major antigenic epitopes on CYP2D6 cDNA have already been identified. To determine whether these antigenic epitopes have conformational or linear structure, the reactivity to full-length recombinant CYP2D6 fusion protein and to four synthetic peptides spanning these four antigenic epitopes on CYP2D6 cDNA was investigated by enzyme-linked immunosorbent assay. A total of 23 sera, positive for anti-LKM-1 by indirect immunofluorescence were studied. Nine sera were negative for anti-HCV antibody and HCV-RNA and the remaining 14 sera were positive for anti-HCV antibody and HCV-RNA. All sera reacted to full-length recombinant CYP2D6 fusion protein. Reactivity to synthetic peptide (aa 257–270), which includes the main epitope on CYP2D6 to anti-LKM-1, was significantly more common in HCV-negative sera than in HCV-positive sera ( P
-
chronic hepatitis c associated with anti liver Kidney Microsome 1 antibody is not a subgroup of autoimmune hepatitis
Journal of Gastroenterology, 1997Co-Authors: Hiroshi Miyakawa, Kazuhiro Abe, Makoto Kako, Eriko Kitazawa, Naomi Kawaguchi, Kentaro Kikuchi, Hirotoshi Fuzikawa, Tatsuji Komatsu, Naoaki Hayashi, Kendo KiyosawaAbstract:To determine whether “autoimmune hepatitis type IIb” should be categorized as a subgroup of autoimmune hepatitis, we conducted a clinicopathological study of 25 adult Japanese patients who were positive for anti-liver/Kidney Microsome-1 (anti-LKM-1) antibody and infected with the hepatitis C virus (HCV). Anti-LKM-1 was determined by indirect immunofluo-rescence and by the double immunodiffusion assays we have developed. Twenty-two patients did not present any unusual symptoms or any associated diseases during the course of their chronic HCV infection. The spectrum of HCV genotypes of these patients did not significantly differ from that of anti-LKM-1-negative Japanese patients with chronic hepatitis C. Histological examination of liver biopsy specimens showed the usual characteristics of chronic hepatitis C and lack of characteristics of autoimmune hepatitis type I. No disease-specific HLA haplotypes were noted, and HLA-DR4, which is detectable in 88.7% of Japanese patients with autoimmune hepatitis type I, was detected in only 50.0% of our group, the same rate as the background frequency. Prednisolone was effective in none of the six patients treated, but interferon was effective in six of ten treated patients (60%). From these results, we conclude that “autoimmune hepatitis type IIb” should not be categorized as autoimmune hepatitis, and that this subgroup is essentially chronic hepatitis C in which an autoantibody has been produced during the course of chronic HCV infection.
