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Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis.
Clin Chim Acta
BACKGROUND: The lack of an immunoassay that detects antibodies to promyelocytic leukaemia (PML) protein, the primary biliary cirrhosis (PBC)-specific multiple nuclear dot (MND) antigen, has prompted us to develop a line immunoassay (LIA) for the simultaneous detection of PML and Sp100 MND-specific autoantibodies. METHODS: PML and Sp100 were expressed in Escherichia coli, and analysed by SDS-PAGE and immunoblotting using a monoclonal antibody and MALDI-ToF fingerprinting. A quantitative PML and Sp100 LIA were developed and testing was performed in 150 anti-mitochondrial antibody (AMA) positive, 20 AMA-PBCs and 130 controls. RESULTS: Thirty-five (23%) of 150 AMA+ PBCs (18 anti-MND+) were anti-PML+ (12%) or anti-Sp100+ (20%), 10 being anti-PML+/Sp100+, 5 single anti-PML+ and 20 single anti-Sp100+. Six (30%, 5 anti-MND+) AMA-PBCs were anti-PML+ or Sp100+. Only 2 (1.7%) pathological controls were anti-PML+ and/or anti-Sp100+. Levels of anti-PML correlated with those of anti-Sp100 (R=0.64, p<0.0001). The autoantibody profile largely remained unchanged over a 10year-follow up (52 patients, 352 samples). Anti-PML, Sp100 or MND-reactive PBCs were younger and had longer disease duration than the seronegative (p=0.06, for both). Anti-Sp100 levels correlated with the Mayo risk score (r=0.63, p=0.01). Anti-PML+/Sp100+ patients had more advanced disease compared to patients negative for anti-PML/Sp100 (p=0.04). CONCLUSION: The new line immunoassay offers a robust and accurate method for the detection of clinically-relevant PBC-specific anti-MND antibodies.
|Title:||Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis.|
|Keywords:||Adult, Amino Acid Sequence, Antibody Specificity, Antigens, Nuclear, Autoantibodies, Autoantigens, Case-Control Studies, Escherichia coli, Follow-Up Studies, Humans, Immunoassay, Leukemia, Promyelocytic, Acute, Liver Cirrhosis, Biliary, Middle Aged, Molecular Sequence Data, Time Factors|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)
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