6533b7d9fe1ef96bd126d6a7
RESEARCH PRODUCT
Identification of cyclin A as a molecular target of antinuclear antibodies (ANA) in hepatic and non-hepatic autoimmune diseases.
Christian BréchotBritta AlexB. LüttigG. GerkenKarl-hermann Meyer Zum BüschenfeldeAufréderique ZindyMichael P. MannsChristian P. Strassburgsubject
AdultPathologymedicine.medical_specialtyAnti-nuclear antibodyCyclin ABlotting WesternImmunoblottingEnzyme-Linked Immunosorbent AssayAutoimmune hepatitisImmunofluorescenceAutoantigensAutoimmune DiseasesMixed connective tissue diseaseimmune system diseasesCyclinsMedicineHumansLupus Erythematosus Systemicskin and connective tissue diseasesFluorescent Antibody Technique IndirectAutoantibodiesAutoimmune diseaseHepatologymedicine.diagnostic_testbiologybusiness.industryLiver DiseasesAutoantibodyDNAMiddle Agedmedicine.diseaseRecombinant ProteinsAntibodies AntinuclearImmunologybiology.proteinAntibodybusinessBaculoviridaedescription
Abstract Background/Aims: Antinuclear antibodies (ANA) are a diagnostic of various autoimmune diseases and also of autoimmune hepatitis type 1. The designation ANA describes a heterogeneous group of autoantibodies. In liver diseases, only a few nuclear target antigens have been molecularly identified and characterized. Cyclins play a central role in a cell cycle regulation, DNA transcription, and cell proliferation. Cyclin A was also identified as an integration site of the hepatitis B virus in a patient with hepatocellular carcinoma. In this study we identify cyclin A as a novel nuclear target protein of ANA. Methods: Sera of patients with autoimmune hepatitis (AIH) type 1 ( n =61), type 2 ( n =21), and type 3 ( n =39), primariy biliary cirrhosis (PBC) ( n =107), rheumatic disease (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), mixed connective tissue disease (MCTD)) ( n =42) and normal controls ( n =100) were evaluated for ANA by indirect immunofluorecence. Baculovirus-generated recombinant human cyclic A protein was used for immunoblotting to study the prevalence of anti-cyclin A autonatibodies in these sera. Results: Sera of patients with AIH type 1 and rheumatic diseases had ANA detected by indirect imunofluorescence. In AIH type 1 12/61 (20%) and in rheumatic diseases 6/42 (14%) were immunoblot positive for autoantibodies against human cyclin A. In PBC, AIH type 3 and normal control sera negative for ANA by immunofluorescence, anti-cyclin A autoantibodies were present in 7–9%; in AIH type 2 and SLE they were undetectable by imunoblot. In some sera a typical cyclin A immunofluorescence was observed. Anti-cyclin A antibodies recognize a 45 and 50 kDa recombinant protein species, providing evidence for the recognition of at least two molecular epitopes. Conclusions: This study has identified cyclin A as a human autoantigen in hepatic and non-hepatic autoimmune diseases. More studies are required to evaluated the clinical and pathophysiological significance of anti-cyclin A autoantibodies. The identification of human anti-cyclin A autoantibodies may additionally become a valuable tool for studying the function and regulation of cyclin A in mammalian and human cells.
year | journal | country | edition | language |
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1996-12-01 | Journal of hepatology |