Comparative Immunoreactivity of Anti-trifluoroacetyl (TFA) Antibody and Anti-lipoic Acid Antibody in Primary Biliary Cirrhosis: Searching for a Mimic
Identifieur interne : 002943 ( Istex/Corpus ); précédent : 002942; suivant : 002944Comparative Immunoreactivity of Anti-trifluoroacetyl (TFA) Antibody and Anti-lipoic Acid Antibody in Primary Biliary Cirrhosis: Searching for a Mimic
Auteurs : Motoko Sasaki ; Aftab Ansari ; Neil Pumford ; Judy Van De Water ; Patrick S. C Leung ; Ken M. Humphries ; Luke I. Szweda ; Yasuni Nakanuma ; Thomas E. Roche ; Ross L. Coppel ; Jean-Francois Bach ; M. Eric GershwinSource :
- Journal of Autoimmunity [ 0896-8411 ] ; 2000.
English descriptors
- KwdEn :
- Antibody, Antimitochondrial autoantibodies, Autoantibody, Autoantibody recognition, Autoantigens, Bile, Bile ducts, Bile ductules, Biliary, Cell injury, Cirrhosis, Clinical immunology, Conformational epitope, Control rats, Coppel, Cytoplasmic, Cytoplasmic staining, Cytoplasmic staining periportal, Cytosolic fractions, Dehydrogenase, Dehydrogenase complexes, Dihydrolipoamide acetyltransferase, Dihydrolipoamide acetyltransferase subunit, Duct, Enzyme activity, Enzyme function, Focal cytoplasmic staining, Free radic, Gershwin, Glycine cleavage protein, Goat antihuman polyvalent, Halothane, Halothane hepatitis, Halothane metabolism, Healthy donors, Hepatitis, Hepatocytes, Hepatology, Higher degree, Human liver, Human liver samples, Human sera, Immune responses, Immunohistochemical staining, Inner lipoyl domain, Lipoic, Lipoic acid, Lipoyl, Lipoyl domain, Lipoyl domains, Lipoylated, Liver section, Liver sections, Liver tissues, Lysine, Lysine residue, Major autoantigen, Milk powder, Mitochondrial, Mitochondrial autoantigens, Mitochondrial enzyme, Mitochondrial proteins, Mitochondrial staining, Molecular mimicry, Monoclonal antibodies, Negative control, Normal rabbit sera, Oxidative stress, Periportal, Periportal hepatocytes, Positive control, Positive staining, Primary biliary cirrhosis, Pyruvate, Pyruvate dehydrogenase, Reaction mixture, Recombinant, Recombinant mitochondrial proteins, Room temperature, Sodium azide, Staining pattern, Subunit, Surgical hepatitis, Weak reactivity, Wild type, primary biliary cirrhosis, halothane, trifluoroacetylated protein, lipoic acid, anti-mitochondrial autoantibody, liver.
- Teeft :
- Antibody, Antimitochondrial autoantibodies, Autoantibody, Autoantibody recognition, Autoantigens, Bile, Bile ducts, Bile ductules, Biliary, Cell injury, Cirrhosis, Clinical immunology, Conformational epitope, Control rats, Coppel, Cytoplasmic, Cytoplasmic staining, Cytoplasmic staining periportal, Cytosolic fractions, Dehydrogenase, Dehydrogenase complexes, Dihydrolipoamide acetyltransferase, Dihydrolipoamide acetyltransferase subunit, Duct, Enzyme activity, Enzyme function, Focal cytoplasmic staining, Free radic, Gershwin, Glycine cleavage protein, Goat antihuman polyvalent, Halothane, Halothane hepatitis, Halothane metabolism, Healthy donors, Hepatitis, Hepatocytes, Hepatology, Higher degree, Human liver, Human liver samples, Human sera, Immune responses, Immunohistochemical staining, Inner lipoyl domain, Lipoic, Lipoic acid, Lipoyl, Lipoyl domain, Lipoyl domains, Lipoylated, Liver section, Liver sections, Liver tissues, Lysine, Lysine residue, Major autoantigen, Milk powder, Mitochondrial, Mitochondrial autoantigens, Mitochondrial enzyme, Mitochondrial proteins, Mitochondrial staining, Molecular mimicry, Monoclonal antibodies, Negative control, Normal rabbit sera, Oxidative stress, Periportal, Periportal hepatocytes, Positive control, Positive staining, Primary biliary cirrhosis, Pyruvate, Pyruvate dehydrogenase, Reaction mixture, Recombinant, Recombinant mitochondrial proteins, Room temperature, Sodium azide, Staining pattern, Subunit, Surgical hepatitis, Weak reactivity, Wild type.
Abstract
Abstract: Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.
Url:
DOI: 10.1006/jaut.2000.0390
Links to Exploration step
ISTEX:DDC8D776E195C4ABD522858946A89814AE0EE8BALe document en format XML
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C" last="Leung">Patrick S. C Leung</name><affiliation><mods:affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</mods:affiliation></affiliation></author><author><name sortKey="Humphries, Ken M" sort="Humphries, Ken M" uniqKey="Humphries K" first="Ken M" last="Humphries">Ken M. Humphries</name><affiliation><mods:affiliation>Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA</mods:affiliation></affiliation></author><author><name sortKey="Szweda, Luke I" sort="Szweda, Luke I" uniqKey="Szweda L" first="Luke I" last="Szweda">Luke I. Szweda</name><affiliation><mods:affiliation>Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA</mods:affiliation></affiliation></author><author><name sortKey="Nakanuma, Yasuni" sort="Nakanuma, Yasuni" uniqKey="Nakanuma Y" first="Yasuni" last="Nakanuma">Yasuni Nakanuma</name><affiliation><mods:affiliation>Department of Pathology, Kanazawa University, Kanazawa, 920, Japan</mods:affiliation></affiliation></author><author><name sortKey="Roche, Thomas E" sort="Roche, Thomas E" uniqKey="Roche T" first="Thomas E" last="Roche">Thomas E. Roche</name><affiliation><mods:affiliation>Department of Biochemistry, Kansas State University, Manhattan, KS, 66506, USA</mods:affiliation></affiliation></author><author><name sortKey="Coppel, Ross L" sort="Coppel, Ross L" uniqKey="Coppel R" first="Ross L" last="Coppel">Ross L. Coppel</name><affiliation><mods:affiliation>Department of Microbiology, Monash University, Clayton, Victoria, 3168, Australia</mods:affiliation></affiliation></author><author><name sortKey="Bach, Jean Francois" sort="Bach, Jean Francois" uniqKey="Bach J" first="Jean-Francois" last="Bach">Jean-Francois Bach</name><affiliation><mods:affiliation>Hopital Necker, 161 rue de Sevres, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Gershwin, M Eric" sort="Gershwin, M Eric" uniqKey="Gershwin M" first="M. Eric" last="Gershwin">M. Eric Gershwin</name><affiliation><mods:affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Autoimmunity</title><title level="j" type="abbrev">YJAUT</title><idno type="ISSN">0896-8411</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000">2000</date><biblScope unit="volume">15</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="51">51</biblScope><biblScope unit="page" to="60">60</biblScope></imprint><idno type="ISSN">0896-8411</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0896-8411</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibody</term><term>Antimitochondrial autoantibodies</term><term>Autoantibody</term><term>Autoantibody recognition</term><term>Autoantigens</term><term>Bile</term><term>Bile ducts</term><term>Bile ductules</term><term>Biliary</term><term>Cell injury</term><term>Cirrhosis</term><term>Clinical immunology</term><term>Conformational epitope</term><term>Control rats</term><term>Coppel</term><term>Cytoplasmic</term><term>Cytoplasmic staining</term><term>Cytoplasmic staining periportal</term><term>Cytosolic fractions</term><term>Dehydrogenase</term><term>Dehydrogenase complexes</term><term>Dihydrolipoamide acetyltransferase</term><term>Dihydrolipoamide acetyltransferase subunit</term><term>Duct</term><term>Enzyme activity</term><term>Enzyme function</term><term>Focal cytoplasmic staining</term><term>Free radic</term><term>Gershwin</term><term>Glycine cleavage protein</term><term>Goat antihuman polyvalent</term><term>Halothane</term><term>Halothane hepatitis</term><term>Halothane metabolism</term><term>Healthy donors</term><term>Hepatitis</term><term>Hepatocytes</term><term>Hepatology</term><term>Higher degree</term><term>Human liver</term><term>Human liver samples</term><term>Human sera</term><term>Immune responses</term><term>Immunohistochemical staining</term><term>Inner lipoyl domain</term><term>Lipoic</term><term>Lipoic acid</term><term>Lipoyl</term><term>Lipoyl domain</term><term>Lipoyl domains</term><term>Lipoylated</term><term>Liver section</term><term>Liver sections</term><term>Liver tissues</term><term>Lysine</term><term>Lysine residue</term><term>Major autoantigen</term><term>Milk powder</term><term>Mitochondrial</term><term>Mitochondrial autoantigens</term><term>Mitochondrial enzyme</term><term>Mitochondrial proteins</term><term>Mitochondrial staining</term><term>Molecular mimicry</term><term>Monoclonal antibodies</term><term>Negative control</term><term>Normal rabbit sera</term><term>Oxidative stress</term><term>Periportal</term><term>Periportal hepatocytes</term><term>Positive control</term><term>Positive staining</term><term>Primary biliary cirrhosis</term><term>Pyruvate</term><term>Pyruvate dehydrogenase</term><term>Reaction mixture</term><term>Recombinant</term><term>Recombinant mitochondrial proteins</term><term>Room temperature</term><term>Sodium azide</term><term>Staining pattern</term><term>Subunit</term><term>Surgical hepatitis</term><term>Weak reactivity</term><term>Wild type</term><term>primary biliary cirrhosis, halothane, trifluoroacetylated protein, lipoic acid, anti-mitochondrial autoantibody, liver</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Antibody</term><term>Antimitochondrial autoantibodies</term><term>Autoantibody</term><term>Autoantibody recognition</term><term>Autoantigens</term><term>Bile</term><term>Bile ducts</term><term>Bile ductules</term><term>Biliary</term><term>Cell injury</term><term>Cirrhosis</term><term>Clinical immunology</term><term>Conformational epitope</term><term>Control rats</term><term>Coppel</term><term>Cytoplasmic</term><term>Cytoplasmic staining</term><term>Cytoplasmic staining periportal</term><term>Cytosolic fractions</term><term>Dehydrogenase</term><term>Dehydrogenase complexes</term><term>Dihydrolipoamide acetyltransferase</term><term>Dihydrolipoamide acetyltransferase subunit</term><term>Duct</term><term>Enzyme activity</term><term>Enzyme function</term><term>Focal cytoplasmic staining</term><term>Free radic</term><term>Gershwin</term><term>Glycine cleavage protein</term><term>Goat antihuman polyvalent</term><term>Halothane</term><term>Halothane hepatitis</term><term>Halothane metabolism</term><term>Healthy donors</term><term>Hepatitis</term><term>Hepatocytes</term><term>Hepatology</term><term>Higher degree</term><term>Human liver</term><term>Human liver samples</term><term>Human sera</term><term>Immune responses</term><term>Immunohistochemical staining</term><term>Inner lipoyl domain</term><term>Lipoic</term><term>Lipoic acid</term><term>Lipoyl</term><term>Lipoyl domain</term><term>Lipoyl domains</term><term>Lipoylated</term><term>Liver section</term><term>Liver sections</term><term>Liver tissues</term><term>Lysine</term><term>Lysine residue</term><term>Major autoantigen</term><term>Milk powder</term><term>Mitochondrial</term><term>Mitochondrial autoantigens</term><term>Mitochondrial enzyme</term><term>Mitochondrial proteins</term><term>Mitochondrial staining</term><term>Molecular mimicry</term><term>Monoclonal antibodies</term><term>Negative control</term><term>Normal rabbit sera</term><term>Oxidative stress</term><term>Periportal</term><term>Periportal hepatocytes</term><term>Positive control</term><term>Positive staining</term><term>Primary biliary cirrhosis</term><term>Pyruvate</term><term>Pyruvate dehydrogenase</term><term>Reaction mixture</term><term>Recombinant</term><term>Recombinant mitochondrial proteins</term><term>Room temperature</term><term>Sodium azide</term><term>Staining pattern</term><term>Subunit</term><term>Surgical hepatitis</term><term>Weak reactivity</term><term>Wild type</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>lipoic</json:string><json:string>cytoplasmic</json:string><json:string>biliary</json:string><json:string>cirrhosis</json:string><json:string>dehydrogenase</json:string><json:string>halothane</json:string><json:string>primary biliary cirrhosis</json:string><json:string>hepatocytes</json:string><json:string>mitochondrial</json:string><json:string>lipoic acid</json:string><json:string>autoantibody</json:string><json:string>lipoyl</json:string><json:string>pyruvate</json:string><json:string>periportal</json:string><json:string>coppel</json:string><json:string>lipoylated</json:string><json:string>recombinant</json:string><json:string>pyruvate dehydrogenase</json:string><json:string>lysine</json:string><json:string>liver tissues</json:string><json:string>room temperature</json:string><json:string>subunit</json:string><json:string>autoantigens</json:string><json:string>hepatology</json:string><json:string>duct</json:string><json:string>bile ducts</json:string><json:string>halothane hepatitis</json:string><json:string>gershwin</json:string><json:string>enzyme activity</json:string><json:string>dehydrogenase complexes</json:string><json:string>glycine cleavage protein</json:string><json:string>immunohistochemical staining</json:string><json:string>inner lipoyl domain</json:string><json:string>molecular mimicry</json:string><json:string>wild type</json:string><json:string>antibody</json:string><json:string>positive control</json:string><json:string>liver section</json:string><json:string>control rats</json:string><json:string>lipoyl domain</json:string><json:string>surgical hepatitis</json:string><json:string>human sera</json:string><json:string>lysine residue</json:string><json:string>liver sections</json:string><json:string>mitochondrial staining</json:string><json:string>positive staining</json:string><json:string>focal cytoplasmic staining</json:string><json:string>hepatitis</json:string><json:string>bile</json:string><json:string>periportal hepatocytes</json:string><json:string>immune responses</json:string><json:string>goat antihuman polyvalent</json:string><json:string>recombinant mitochondrial proteins</json:string><json:string>normal rabbit sera</json:string><json:string>reaction mixture</json:string><json:string>conformational epitope</json:string><json:string>higher degree</json:string><json:string>human liver samples</json:string><json:string>healthy donors</json:string><json:string>cytoplasmic staining</json:string><json:string>human liver</json:string><json:string>free radic</json:string><json:string>sodium azide</json:string><json:string>staining pattern</json:string><json:string>weak reactivity</json:string><json:string>negative control</json:string><json:string>cytosolic fractions</json:string><json:string>milk powder</json:string><json:string>cytoplasmic staining periportal</json:string><json:string>enzyme function</json:string><json:string>mitochondrial proteins</json:string><json:string>autoantibody recognition</json:string><json:string>lipoyl domains</json:string><json:string>oxidative stress</json:string><json:string>cell injury</json:string><json:string>monoclonal antibodies</json:string><json:string>mitochondrial enzyme</json:string><json:string>mitochondrial autoantigens</json:string><json:string>dihydrolipoamide acetyltransferase</json:string><json:string>antimitochondrial autoantibodies</json:string><json:string>major autoantigen</json:string><json:string>dihydrolipoamide acetyltransferase subunit</json:string><json:string>clinical immunology</json:string><json:string>halothane metabolism</json:string><json:string>bile ductules</json:string></teeft></keywords><author><json:item><name>Motoko Sasaki</name><affiliations><json:string>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</json:string></affiliations></json:item><json:item><name>Aftab Ansari</name><affiliations><json:string>Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA</json:string></affiliations></json:item><json:item><name>Neil Pumford</name><affiliations><json:string>Department of Pharmacology, University of Arkansas, Fayetteville, Arkansas, 72701, USA</json:string></affiliations></json:item><json:item><name>Judy van de Water</name><affiliations><json:string>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</json:string></affiliations></json:item><json:item><name>Patrick S.C Leung</name><affiliations><json:string>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</json:string></affiliations></json:item><json:item><name>Ken M Humphries</name><affiliations><json:string>Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA</json:string></affiliations></json:item><json:item><name>Luke I Szweda</name><affiliations><json:string>Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA</json:string></affiliations></json:item><json:item><name>Yasuni Nakanuma</name><affiliations><json:string>Department of Pathology, Kanazawa University, Kanazawa, 920, Japan</json:string></affiliations></json:item><json:item><name>Thomas E Roche</name><affiliations><json:string>Department of Biochemistry, Kansas State University, Manhattan, KS, 66506, USA</json:string></affiliations></json:item><json:item><name>Ross L Coppel</name><affiliations><json:string>Department of Microbiology, Monash University, Clayton, Victoria, 3168, Australia</json:string></affiliations></json:item><json:item><name>Jean-Francois Bach</name><affiliations><json:string>Hopital Necker, 161 rue de Sevres, Paris, France</json:string></affiliations></json:item><json:item><name>M.Eric Gershwin</name><affiliations><json:string>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>primary biliary cirrhosis, halothane, trifluoroacetylated protein, lipoic acid, anti-mitochondrial autoantibody, liver</value></json:item></subject><arkIstex>ark:/67375/6H6-CMV6BRPJ-P</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.</abstract><qualityIndicators><score>10</score><pdfWordCount>5193</pdfWordCount><pdfCharCount>35257</pdfCharCount><pdfVersion>1.4</pdfVersion><pdfPageCount>10</pdfPageCount><pdfPageSize>595 x 794 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>288</abstractWordCount><abstractCharCount>1979</abstractCharCount><keywordCount>1</keywordCount></qualityIndicators><title>Comparative Immunoreactivity of Anti-trifluoroacetyl (TFA) Antibody and Anti-lipoic Acid Antibody in Primary Biliary Cirrhosis: Searching for a Mimic</title><pmid><json:string>10936028</json:string></pmid><pii><json:string>S0896-8411(00)90390-1</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Journal of Autoimmunity</title><language><json:string>unknown</json:string></language><publicationDate>2000</publicationDate><issn><json:string>0896-8411</json:string></issn><pii><json:string>S0896-8411(00)X0010-8</json:string></pii><volume>15</volume><issue>1</issue><pages><first>51</first><last>60</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2000</json:string></date><geogName></geogName><orgName><json:string>Institute of Enzyme Research, University of Tokushima, Japan</json:string><json:string>DAKO Corp., Santa Barbara</json:string><json:string>Biochemica</json:string><json:string>Department of Physiology and Biophysics</json:string><json:string>Case Western Reserve University</json:string><json:string>Division of Rheumatology</json:string><json:string>Department of Biochemistry, Kansas State University, Manhattan, KS</json:string><json:string>Department of Pharmacology, University of Arkansas, Fayetteville, Arkansas</json:string><json:string>Department of Pathology, Kanazawa University, Kanazawa</json:string><json:string>New Zealand White</json:string><json:string>Antibodies Inc.</json:string><json:string>Sigma Chemical Co.</json:string><json:string>Department of Pathology, Emory University School of Medicine, Atlanta, GA</json:string><json:string>University of California</json:string><json:string>France Received</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Thomas E. Roche</json:string><json:string>Jean-Francois Bach</json:string><json:string>Luke I. Szweda</json:string><json:string>M. Eric</json:string><json:string>Ken M. Humphries</json:string><json:string>Van de Water</json:string><json:string>ELISA Figure</json:string><json:string>Ross L. Coppel</json:string><json:string>Neil Pumford</json:string><json:string>Y. Motokowa</json:string><json:string>Lance Pohl</json:string><json:string>S. C. Leung</json:string></persName><placeName><json:string>Germany</json:string><json:string>Australia</json:string><json:string>Davis</json:string><json:string>Hamburg</json:string><json:string>USA</json:string><json:string>Japan</json:string><json:string>San Francisco</json:string><json:string>CA</json:string><json:string>Denver</json:string><json:string>Mountain View</json:string><json:string>OH</json:string><json:string>PA</json:string></placeName><ref_url><json:string>http://www.idealibrary.com</json:string></ref_url><ref_bibl><json:string>[25, 26]</json:string><json:string>[12]</json:string><json:string>Frey et al.</json:string><json:string>[34, 35]</json:string><json:string>[5, 23]</json:string><json:string>[33]</json:string><json:string>[19, 20]</json:string><json:string>[9, 11]</json:string><json:string>[10]</json:string><json:string>[5]</json:string><json:string>[30]</json:string><json:string>[36]</json:string><json:string>[31, 32]</json:string><json:string>M. Sasaki et al.</json:string><json:string>[13, 14, 29]</json:string><json:string>Department of Microbiology, Monash University, Clayton, Victoria, 3168</json:string><json:string>[24]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-CMV6BRPJ-P</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - immunology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - immunology</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - Immunology</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Immunology and Allergy</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string><json:string>4 - gastroenterologie. foie. pancreas. abdomen</json:string></inist></categories><publicationDate>2000</publicationDate><copyrightDate>2000</copyrightDate><doi><json:string>10.1006/jaut.2000.0390</json:string></doi><id>DDC8D776E195C4ABD522858946A89814AE0EE8BA</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/DDC8D776E195C4ABD522858946A89814AE0EE8BA/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/DDC8D776E195C4ABD522858946A89814AE0EE8BA/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/DDC8D776E195C4ABD522858946A89814AE0EE8BA/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Comparative Immunoreactivity of Anti-trifluoroacetyl (TFA) Antibody and Anti-lipoic Acid Antibody in Primary Biliary Cirrhosis: Searching for a Mimic</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>©2000 Academic Press</p></availability><date>2000</date></publicationStmt><notesStmt><note type="content">Section title: Regular Article</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Comparative Immunoreactivity of Anti-trifluoroacetyl (TFA) Antibody and Anti-lipoic Acid Antibody in Primary Biliary Cirrhosis: Searching for a Mimic</title><author xml:id="author-0000"><persName><forename type="first">Motoko</forename><surname>Sasaki</surname></persName><affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Aftab</forename><surname>Ansari</surname></persName><affiliation>Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Neil</forename><surname>Pumford</surname></persName><affiliation>Department of Pharmacology, University of Arkansas, Fayetteville, Arkansas, 72701, USA</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Judy</forename><surname>van de Water</surname></persName><affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Patrick S.C</forename><surname>Leung</surname></persName><affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Ken M</forename><surname>Humphries</surname></persName><affiliation>Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Luke I</forename><surname>Szweda</surname></persName><affiliation>Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Yasuni</forename><surname>Nakanuma</surname></persName><affiliation>Department of Pathology, Kanazawa University, Kanazawa, 920, Japan</affiliation></author><author xml:id="author-0008"><persName><forename type="first">Thomas E</forename><surname>Roche</surname></persName><affiliation>Department of Biochemistry, Kansas State University, Manhattan, KS, 66506, USA</affiliation></author><author xml:id="author-0009"><persName><forename type="first">Ross L</forename><surname>Coppel</surname></persName><affiliation>Department of Microbiology, Monash University, Clayton, Victoria, 3168, Australia</affiliation></author><author xml:id="author-0010"><persName><forename type="first">Jean-Francois</forename><surname>Bach</surname></persName><affiliation>Hopital Necker, 161 rue de Sevres, Paris, France</affiliation></author><author xml:id="author-0011"><persName><forename type="first">M.Eric</forename><surname>Gershwin</surname></persName><note type="correspondence"><p>Correspondence to: M. Eric Gershwin, M.D., Division of Rheumatology, Allergy, and Clinical Immunology, University of California, School of Medicine, TB 192, One Shields Avenue, Davis, CA 95616, USA. Fax: 530-752-4669. E-mail:megershwin@ucdavis.edu</p></note><affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</affiliation></author><idno type="istex">DDC8D776E195C4ABD522858946A89814AE0EE8BA</idno><idno type="DOI">10.1006/jaut.2000.0390</idno><idno type="PII">S0896-8411(00)90390-1</idno></analytic><monogr><title level="j">Journal of Autoimmunity</title><title level="j" type="abbrev">YJAUT</title><idno type="pISSN">0896-8411</idno><idno type="PII">S0896-8411(00)X0010-8</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000"></date><biblScope unit="volume">15</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="51">51</biblScope><biblScope unit="page" to="60">60</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2000</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>primary biliary cirrhosis, halothane, trifluoroacetylated protein, lipoic acid, anti-mitochondrial autoantibody, liver</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2000">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/DDC8D776E195C4ABD522858946A89814AE0EE8BA/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>YJAUT</jid><aid>90390</aid><ce:pii>S0896-8411(00)90390-1</ce:pii><ce:doi>10.1006/jaut.2000.0390</ce:doi><ce:copyright type="full-transfer" year="2000">Academic Press</ce:copyright></item-info><head><ce:dochead><ce:textfn>Regular Article</ce:textfn></ce:dochead><ce:title>Comparative Immunoreactivity of Anti-trifluoroacetyl (TFA) Antibody and Anti-lipoic Acid Antibody in Primary Biliary Cirrhosis: Searching for a Mimic</ce:title><ce:author-group><ce:author><ce:given-name>Motoko</ce:given-name><ce:surname>Sasaki</ce:surname><ce:cross-ref refid="A1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Aftab</ce:given-name><ce:surname>Ansari</ce:surname><ce:cross-ref refid="A2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Neil</ce:given-name><ce:surname>Pumford</ce:surname><ce:cross-ref refid="A3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Judy</ce:given-name><ce:surname>van de Water</ce:surname><ce:cross-ref refid="A1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Patrick S.C</ce:given-name><ce:surname>Leung</ce:surname><ce:cross-ref refid="A1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Ken M</ce:given-name><ce:surname>Humphries</ce:surname><ce:cross-ref refid="A4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Luke I</ce:given-name><ce:surname>Szweda</ce:surname><ce:cross-ref refid="A4"><ce:sup>d</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Yasuni</ce:given-name><ce:surname>Nakanuma</ce:surname><ce:cross-ref refid="A5"><ce:sup>e</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Thomas E</ce:given-name><ce:surname>Roche</ce:surname><ce:cross-ref refid="A6"><ce:sup>f</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Ross L</ce:given-name><ce:surname>Coppel</ce:surname><ce:cross-ref refid="A7"><ce:sup>g</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Jean-Francois</ce:given-name><ce:surname>Bach</ce:surname><ce:cross-ref refid="A8"><ce:sup>h</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>M.Eric</ce:given-name><ce:surname>Gershwin</ce:surname><ce:cross-ref refid="A1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="FN1"><ce:sup>f1</ce:sup><ce:footnote id="FN1"><ce:label>f1</ce:label><ce:note-para>Correspondence to: M. Eric Gershwin, M.D., Division of Rheumatology, Allergy, and Clinical Immunology, University of California, School of Medicine, TB 192, One Shields Avenue, Davis, CA 95616, USA. Fax: 530-752-4669. E-mail:megershwin@ucdavis.edu</ce:note-para></ce:footnote></ce:cross-ref></ce:author><ce:affiliation id="A1"><ce:label>a</ce:label><ce:textfn>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</ce:textfn></ce:affiliation><ce:affiliation id="A2"><ce:label>b</ce:label><ce:textfn>Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA</ce:textfn></ce:affiliation><ce:affiliation id="A3"><ce:label>c</ce:label><ce:textfn>Department of Pharmacology, University of Arkansas, Fayetteville, Arkansas, 72701, USA</ce:textfn></ce:affiliation><ce:affiliation id="A4"><ce:label>d</ce:label><ce:textfn>Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA</ce:textfn></ce:affiliation><ce:affiliation id="A5"><ce:label>e</ce:label><ce:textfn>Department of Pathology, Kanazawa University, Kanazawa, 920, Japan</ce:textfn></ce:affiliation><ce:affiliation id="A6"><ce:label>f</ce:label><ce:textfn>Department of Biochemistry, Kansas State University, Manhattan, KS, 66506, USA</ce:textfn></ce:affiliation><ce:affiliation id="A7"><ce:label>g</ce:label><ce:textfn>Department of Microbiology, Monash University, Clayton, Victoria, 3168, Australia</ce:textfn></ce:affiliation><ce:affiliation id="A8"><ce:label>h</ce:label><ce:textfn>Hopital Necker, 161 rue de Sevres, Paris, France</ce:textfn></ce:affiliation></ce:author-group><ce:date-received day="10" month="3" year="2000"></ce:date-received><ce:date-accepted day="29" month="5" year="2000"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para id="simple-para0005">Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>primary biliary cirrhosis, halothane, trifluoroacetylated protein, lipoic acid, anti-mitochondrial autoantibody, liver</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Comparative Immunoreactivity of Anti-trifluoroacetyl (TFA) Antibody and Anti-lipoic Acid Antibody in Primary Biliary Cirrhosis: Searching for a Mimic</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Comparative Immunoreactivity of Anti-trifluoroacetyl (TFA) Antibody and Anti-lipoic Acid Antibody in Primary Biliary Cirrhosis: Searching for a Mimic</title></titleInfo><name type="personal"><namePart type="given">Motoko</namePart><namePart type="family">Sasaki</namePart><affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Aftab</namePart><namePart type="family">Ansari</namePart><affiliation>Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Neil</namePart><namePart type="family">Pumford</namePart><affiliation>Department of Pharmacology, University of Arkansas, Fayetteville, Arkansas, 72701, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Judy</namePart><namePart type="family">van de Water</namePart><affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrick S.C</namePart><namePart type="family">Leung</namePart><affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ken M</namePart><namePart type="family">Humphries</namePart><affiliation>Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Luke I</namePart><namePart type="family">Szweda</namePart><affiliation>Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yasuni</namePart><namePart type="family">Nakanuma</namePart><affiliation>Department of Pathology, Kanazawa University, Kanazawa, 920, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas E</namePart><namePart type="family">Roche</namePart><affiliation>Department of Biochemistry, Kansas State University, Manhattan, KS, 66506, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ross L</namePart><namePart type="family">Coppel</namePart><affiliation>Department of Microbiology, Monash University, Clayton, Victoria, 3168, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean-Francois</namePart><namePart type="family">Bach</namePart><affiliation>Hopital Necker, 161 rue de Sevres, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.Eric</namePart><namePart type="family">Gershwin</namePart><affiliation>Division of Rheumatology/Allergy and Clinical Immunology, University of California at Davis, Davis, CA, 95616, USA</affiliation><description>Correspondence to: M. Eric Gershwin, M.D., Division of Rheumatology, Allergy, and Clinical Immunology, University of California, School of Medicine, TB 192, One Shields Avenue, Davis, CA 95616, USA. Fax: 530-752-4669. E-mail:megershwin@ucdavis.edu</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued><copyrightDate encoding="w3cdtf">2000</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.</abstract><note type="content">Section title: Regular Article</note><subject lang="en"><genre>Keywords</genre><topic>primary biliary cirrhosis, halothane, trifluoroacetylated protein, lipoic acid, anti-mitochondrial autoantibody, liver</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Autoimmunity</title></titleInfo><titleInfo type="abbreviated"><title>YJAUT</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">200008</dateIssued></originInfo><identifier type="ISSN">0896-8411</identifier><identifier type="PII">S0896-8411(00)X0010-8</identifier><part><date>200008</date><detail type="volume"><number>15</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue-pages"><start>1</start><end>80</end></extent><extent unit="pages"><start>51</start><end>60</end></extent></part></relatedItem><identifier type="istex">DDC8D776E195C4ABD522858946A89814AE0EE8BA</identifier><identifier type="ark">ark:/67375/6H6-CMV6BRPJ-P</identifier><identifier type="DOI">10.1006/jaut.2000.0390</identifier><identifier type="PII">S0896-8411(00)90390-1</identifier><accessCondition type="use and reproduction" contentType="copyright">©2000 Academic Press</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Academic Press, ©2000</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/DDC8D776E195C4ABD522858946A89814AE0EE8BA/metadata/json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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