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

Maria G. Mytilinaiou; Wolfgang Meyer; Thomas Scheper; Eirini I. Rigopoulou; Christian Probst; Andreas L. Koutsoumpas; Daniel Abeles; Andrew K. Burroughs; Lars Komorowski; Diego Vergani; Dimitrios P. Bogdanos

doi:10.1016/j.cca.2012.03.020

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

Maria G. Mytilinaiou, Wolfgang Meyer, Thomas Scheper, Eirini I. Rigopoulou, Christian Probst, Andreas L. Koutsoumpas, Daniel Abeles, Andrew K. Burroughs, Lars Komorowski, Diego Vergani, Dimitrios P. Bogdanos

King's College London

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

Abstract

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 SOS-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).

Original language	English
Pages (from-to)	1211-1216
Number of pages	6
Journal	Clinica Chimica Acta
Volume	413
Issue number	15-16
DOIs	https://doi.org/10.1016/j.cca.2012.03.020
Publication status	Published - 16 Aug 2012

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10.1016/j.cca.2012.03.020

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Mytilinaiou, M. G., Meyer, W., Scheper, T., Rigopoulou, E. I., Probst, C., Koutsoumpas, A. L., Abeles, D., Burroughs, A. K., Komorowski, L., Vergani, D., & Bogdanos, D. P. (2012). Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis. Clinica Chimica Acta, 413(15-16), 1211-1216. https://doi.org/10.1016/j.cca.2012.03.020

@article{e923cec576f84f0b9f1c3993d5a80924,

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

abstract = "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 SOS-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. (C) 2012 Elsevier B.V. All rights reserved.",

author = "Mytilinaiou, {Maria G.} and Wolfgang Meyer and Thomas Scheper and Rigopoulou, {Eirini I.} and Christian Probst and Koutsoumpas, {Andreas L.} and Daniel Abeles and Burroughs, {Andrew K.} and Lars Komorowski and Diego Vergani and Bogdanos, {Dimitrios P.}",

year = "2012",

month = aug,

day = "16",

doi = "10.1016/j.cca.2012.03.020",

language = "English",

volume = "413",

pages = "1211--1216",

journal = "Clinica Chimica Acta",

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}

Mytilinaiou, MG, Meyer, W, Scheper, T, Rigopoulou, EI, Probst, C, Koutsoumpas, AL , Abeles, D, Burroughs, AK, Komorowski, L, Vergani, D & Bogdanos, DP 2012, 'Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis', Clinica Chimica Acta, vol. 413, no. 15-16, pp. 1211-1216. https://doi.org/10.1016/j.cca.2012.03.020

TY - JOUR

T1 - Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis

AU - Mytilinaiou, Maria G.

AU - Meyer, Wolfgang

AU - Scheper, Thomas

AU - Rigopoulou, Eirini I.

AU - Probst, Christian

AU - Koutsoumpas, Andreas L.

AU - Abeles, Daniel

AU - Burroughs, Andrew K.

AU - Komorowski, Lars

AU - Vergani, Diego

AU - Bogdanos, Dimitrios P.

PY - 2012/8/16

Y1 - 2012/8/16

N2 - 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 SOS-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. (C) 2012 Elsevier B.V. All rights reserved.

AB - 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 SOS-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. (C) 2012 Elsevier B.V. All rights reserved.

U2 - 10.1016/j.cca.2012.03.020

DO - 10.1016/j.cca.2012.03.020

M3 - Article

SN - 0009-8981

VL - 413

SP - 1211

EP - 1216

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

IS - 15-16

ER -

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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