Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis

Lapierre, Pascal; Hajoui, O.; Homberg, Jean‐Claude; Álvarez, Fernando

doi:10.1016/s0016-5085(99)70186-1

Cited by 220 publications

(138 citation statements)

References 13 publications

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“…Type 1 AIH is characterized by the presence of anti-nuclear antibodies (ANA) and/or antismooth muscle antibodies (SMA) and/or anti-soluble liver antigen (SLA) [6,7] . Type 2 AIH patients are defined by the presence of circulating anti-liver-kidney microsome antibodies (LKM1) and/or anti-liver cytosol 1 antibodies (LC1) [8,9] . Anti-LKM1 antibodies recognize the cytochrome P4502D6 (CYP2D6) [10] and anti-LC1 antibodies react against the formiminotransferase cyclodeaminase (FTCD) [9] .…”

Section: Autoimmune Hepatitis: An Overviewmentioning

confidence: 99%

Influence of genes, sex, age and environment on the onset of autoimmune hepatitis

Béland¹,

Lapierre²,

Álvarez³

2009

WJG

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Section: Autoimmune Hepatitis: An Overviewmentioning

confidence: 99%

Influence of genes, sex, age and environment on the onset of autoimmune hepatitis

Béland¹,

Lapierre²,

Álvarez³

2009

WJG

Self Cite

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“…6 In a recent report, Lapierre et al after screening a complementary DNA (cDNA) library of HepG2 cells with an LC1-positive serum isolated a clone with high sequence homology to pig formiminotransferase cyclodeaminase (FTCD), and showed that a construct encoding the C-terminal portion of FTCD can be recognized by LC1 antibodies. 7 FTCD is a mammalian metabolic enzyme involved in the conversion of histidine to glutamic acid, 8 and is most highly expressed in the liver. FTCD is bifunctional and is composed of distinct FT and CD domains connected by a short linker.…”

mentioning

confidence: 99%

Distinct epitopes on formiminotransferase cyclodeaminase induce autoimmune liver cytosol antibody type 1

Muratori

2001

Hepatology

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Liver cytosol antibody type 1 (LC1) is regarded as a serologic marker of type 2 autoimmune hepatitis, in addition to liver kidney microsomal antibody type 1. Among 38 patients with type 2 autoimmune hepatitis, 23 were positive for LC1 antibodies. The antigen recognized by LC1 has been identified as a liver-specific 58-kd metabolic enzyme named formiminotransferase cyclodeaminase (FTCD). All 23 LC1-positive sera immunoprecipitated rat FTCD, and 22 gave an identity reaction with rat FTCD by immunodiffusion. No reaction was observed with sera from 10 patients with type 1 autoimmune hepatitis, 10 with primary biliary cirrhosis, 10 with chronic hepatitis C, and 10 healthy controls. By Western immunoblotting all 23 LC1-positive sera and all the controls tested negative, suggesting that all the antigenic epitopes were destroyed by denaturation. Liver cytosol antibody type 1 (LC1) has been first described, alone or in association with liver kidney microsomal antibody type 1 (LKM1), in patients with type 2 autoimmune hepatitis. 1,2 Only sporadically is it detected in patients with chronic hepatitis C virus infection, usually in association with LKM1. 3,4 Among the different autoantibodies deemed as serologic markers of autoimmune hepatitis, 5 LC1 is particularly intriguing because it targets a liver-specific antigen. 1,2 In addition, serum LC1 concentrations appear to fluctuate in parallel with aminotransferase levels, an observation that suggests a possible role of LC1 autoreactivity in the pathogenic mechanisms leading to hepatocyte injury. 6 In a recent report, Lapierre et al. after screening a complementary DNA (cDNA) library of HepG2 cells with an LC1-positive serum isolated a clone with high sequence homology to pig formiminotransferase cyclodeaminase (FTCD), and showed that a construct encoding the C-terminal portion of FTCD can be recognized by LC1 antibodies. 7 FTCD is a mammalian metabolic enzyme involved in the conversion of histidine to glutamic acid, 8 and is most highly expressed in the liver. FTCD is bifunctional and is composed of distinct FT and CD domains connected by a short linker. The FT activity transfers a formimino group from N-formimino-L-glutamic acid to tetrahydrofolate to generate glutamic acid and 5-formiminotetrahydrofolate, and the CD activity then converts the 5-formiminotetrahydrofolate to 5,10-methenyl tetrahydrofolate and ammonia. Native FTCD is an octamer with 8 identical subunits arranged in a planar ring. 8 FTCD is a soluble cytosolic protein, but in cells appears to be preferentially associated with the cytosolic side of Golgi membranes. [9][10][11] In addition, FTCD appears to be a dynamic component of the Golgi, and cycles between the Golgi and earlier compartments of secretory pathways. 9 In this report, we show that a human liver cytosol protein immunoprecipitated with a pool of LC1-positive autoimmune sera is FTCD, and that LC1 sera recognize distinct epitopes on FTCD. We used full-length recombinant rat FTCD as antigenic substratum for immunodiffusion, immunoblotting, and immu...

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“…Lenzi et al have also found anti-LC1 antibodies in 14% anti-LKM-1 antibody positive patients suffering from chronic hepatitis C virus infection [36] . The enzyme formiminotransferase cyclodeaminase (FTCD) has been identified as the molecular target of anti-LC1 antibodies [37,38] .…”

Section: Liver Cytosol Antibody (Anti-lc1)mentioning

confidence: 99%

“…ELISAs for detection of antibodies to FTCD, the target of anti-LC1, have been developed and used in diagnostic laboratories and their diagnostic and clinical relevance is under investigation [37,38] .…”

Section: Lc1 Antigenmentioning

confidence: 99%

Autoimmune liver serology: Current diagnostic and clinical challenges

Bogdanos¹,

Invernizzi²,

Mackay³

et al. 2008

WJG

193

170

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Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and nonspecific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians' requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.

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Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis

Cited by 220 publications

References 13 publications

Influence of genes, sex, age and environment on the onset of autoimmune hepatitis

Influence of genes, sex, age and environment on the onset of autoimmune hepatitis

Distinct epitopes on formiminotransferase cyclodeaminase induce autoimmune liver cytosol antibody type 1

Autoimmune liver serology: Current diagnostic and clinical challenges

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