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Fernando Alvarez - One of the best experts on this subject based on the ideXlab platform.
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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
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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
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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.
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identification of the main epitope on human cytochrome p450 iid6 recognized by anti liver kidney Microsome Antibody
Journal of Autoimmunity, 1991Co-Authors: M Gueguen, Olivier Bernard, Odile Boniface, François Clerc, Terence Cartwright, Fernando AlvarezAbstract:Abstract Antibodies present in the sera of a group of children with autoimmune hepatitis react with human cytochrome P450 IID6. cDNA constructions of various fragments of human P450 IID6 were made and expressed and the resulting peptides were tested in immunoblot with patients' sera. These allowed identification of at least two antigenic sites on the P450 molecule. The main one, recognized by all sera tested, is located between amino acids 239 and 271. Synthesis of three peptides covering this area of the molecule allowed identification of a sequence of three amino acids (tyrosine—tryptophane—asparagine) located at position 261–263 that constitutes the essential part of the epitope. A protein sequence data-base search revealed homologies between this region of human P450 and proteins from Salmonella typhimurium , from human T lymphotropic virus types 1 and 2 and Herpes simplex virus type 1.
Jean-marie Huraux - One of the best experts on this subject based on the ideXlab platform.
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liver kidney Microsome Antibody type 1 and hepatitis c virus infection
Hepatology, 1992Co-Authors: Francloise Lunel, N. Abuaf, Lionel Frangeul, Patrick Grippon, Michèle Perrin, Dominique Valla, Eric Borotto, Yann Le Coz, Annemarie Yamamoto, Jean-marie HurauxAbstract:Recent studies have shown that hepatitis C virus antibodies are present in a large proportion of patients with autoimmune hepatitis type 2. We have studied 83 patients with liver/kidney Microsome Antibody-positive type 1 hepatitis. Hepatitis C virus antibodies were sought in every case by second-generation tests (hepatitis C virus enzyme-linked immunosorbent assay and recombinant immunoblot assay). Hepatitis C virus RNA sequences were sought in 22 patients (12 with recombinant immunoblot assay-positive results and 10 with recombinant immunoblot assay-negative results) by means of polymerase chain reaction and by use of primers located in the 5′ noncoding region. Sixty-four patients (77%) had positive results for hepatitis C virus antibodies in the enzyme-linked immunosorbent assay test, and 41 (49.3%) were confirmed by recombinant immunoblot assay. Hepatitis C virus RNA sequences were found in all the recombinant immunoblot assaypositive patients but in none of the 10 who were recombinant immunoblot assay-negative. The recombinant immunoblot assay-negative patients were younger than those who were positive (13 ± 11 vs. 50 ± 11 years) and had higher γ-globulin levels and liver/kidney Microsome Antibody-positive type 1 titers (61% had a titer of 1:1,000 or more, vs. only 17% of the recombinant immunoblot assay-positive patients). On the basis of these results, chronic hepatitis with liver/kidney Microsome Antibody-positive type 1 can be divided into two subgroups: (a) true autoimmune hepatitis type 2 (mainly observed in young women), with high titers of liver/kidney Microsome Antibody-positive type 1, and in which direct autoimmune mechanisms appear to be prominent; and (b) hepatitis C virus-associated hepatitis with liver/kidney Microsome Antibody-positive type 1 (generally affecting older patients, especially men), with low titers of liver/kidney Microsome Antibody-positive type 1, and in which the autoimmune process could be a consequence of hepatitis C virus infection. (HEPATOLOGY 1992;16:630–636.)
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Liver/kidney Microsome Antibody type 1 and hepatitis C virus infection
Hepatology (Baltimore Md.), 1992Co-Authors: Francloise Lunel, N. Abuaf, Lionel Frangeul, Patrick Grippon, Michèle Perrin, Yann Le Coz, Dominique Valla, Eric Borotto, Anne‐marie Yamamoto, Jean-marie HurauxAbstract:Recent studies have shown that hepatitis C virus antibodies are present in a large proportion of patients with autoimmune hepatitis type 2. We have studied 83 patients with liver/kidney Microsome Antibody-positive type 1 hepatitis. Hepatitis C virus antibodies were sought in every case by second-generation tests (hepatitis C virus enzyme-linked immunosorbent assay and recombinant immunoblot assay). Hepatitis C virus RNA sequences were sought in 22 patients (12 with recombinant immunoblot assay-positive results and 10 with recombinant immunoblot assay-negative results) by means of polymerase chain reaction and by use of primers located in the 5′ noncoding region. Sixty-four patients (77%) had positive results for hepatitis C virus antibodies in the enzyme-linked immunosorbent assay test, and 41 (49.3%) were confirmed by recombinant immunoblot assay. Hepatitis C virus RNA sequences were found in all the recombinant immunoblot assaypositive patients but in none of the 10 who were recombinant immunoblot assay-negative. The recombinant immunoblot assay-negative patients were younger than those who were positive (13 ± 11 vs. 50 ± 11 years) and had higher γ-globulin levels and liver/kidney Microsome Antibody-positive type 1 titers (61% had a titer of 1:1,000 or more, vs. only 17% of the recombinant immunoblot assay-positive patients). On the basis of these results, chronic hepatitis with liver/kidney Microsome Antibody-positive type 1 can be divided into two subgroups: (a) true autoimmune hepatitis type 2 (mainly observed in young women), with high titers of liver/kidney Microsome Antibody-positive type 1, and in which direct autoimmune mechanisms appear to be prominent; and (b) hepatitis C virus-associated hepatitis with liver/kidney Microsome Antibody-positive type 1 (generally affecting older patients, especially men), with low titers of liver/kidney Microsome Antibody-positive type 1, and in which the autoimmune process could be a consequence of hepatitis C virus infection. (HEPATOLOGY 1992;16:630–636.)
Ana M. Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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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.
Jean-claude Homberg - One of the best experts on this subject based on the ideXlab platform.
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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
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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.
Dominique Charles Belli - One of the best experts on this subject based on the ideXlab platform.
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Anti-liver-kidney Microsome Antibody-positive autoimmune hepatitis associated with alopecia.
Journal of pediatric gastroenterology and nutrition, 1991Co-Authors: Virginie Chaves, Nisen Abuaf, Luc Paunier, Raymond Berclaz, Guy Délèze, Dominique Charles BelliAbstract:A 14-year-old girl presented with anti-liver-kidney Microsome autoimmune hepatitis preceded by alopecia 3 years earlier. Both pathologies were greatly improved by immunosuppressive therapy. Alopecia is a newly reported extrahepatic manifestation of type 2 autoimmune hepatitis. Its appearance could alert the clinician to an increased risk of autoimmune hepatitis in children.