Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis

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• 作者：Maria G. Mytilinaiou^a ; ^b ; Wolfgang Meyer^c ; Thomas Scheper^c ; Eirini I. Rigopoulou^d ; Christian Probst^c ; Andreas L. Koutsoumpas^a ; ^b ; Daniel Abeles^a ; Andrew K. Burroughs^e ; Lars Komorowski^c ; ¹ ; Diego Vergani^a ; Dimitrios P. Bogdanos^a ; ^b ; ^d ; ¹ ; ^{dimitrios.bogdanos@kcl.ac.uk} ;
• 关键词：Anti-nuclear antibody ; Autoimmunity ; Autoimmune liver disease ; Autoimmune hepatitis ; Cholestasis ; Nuclear dots
• 刊名：Clinica Chimica Acta
• 出版年：2012
• 期刊代码：54_00098981
• 类别：med
• 出版时间：16 August, 2012
• 卷：413
• 期：15-16
• 页码：1211-1216
• 文件大小：432 K

摘要

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 10 year-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.