Ann Lab Med.  2019 May;39(3):291-298. 10.3343/alm.2019.39.3.291.

Detection of Autoantibodies Against Nucleoporin p62 in Sera of Patients With Primary Biliary Cholangitis

• Bauer A
• Habior A

• KMID: 2431607
• DOI: http://doi.org/10.3343/alm.2019.39.3.291

Abstract

BACKGROUND
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by specific autoantibodies. We evaluated the prevalence of autoantibodies against nucleoporin p62 (anti-p62) in PBC patients' sera to determine whether it can be a marker for PBC, in comparison with other immunological and biochemical parameters. We validated the performance of our in-house ELISA technique.
METHODS
Serum samples were collected from 135 PBC patients. Thirty patients with primary sclerosing cholangitis (PSC) and 30 with autoimmune hepatitis (AIH) were included as pathological controls, and 40 healthy blood donors served as healthy controls. The presence of anti-p62 was determined by an in-house ELISA using a recombinant protein. We calculated the sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratio (LR+ and LR−) of our in-house ELISA for diagnosing PBC based on anti-p62. Findings were correlated with biochemical data and survival.
RESULTS
Anti-p62 was detected in 32 PBC patients (23.7%). Specificity and PPV of anti-p62 for PBC were 99% and 97%, respectively. The difference between proportions of anti-p62-positive patients and controls was 0.23 (95% confidence interval [CI]: 0.03-0.40; P < 0.0001); LR+ and LR− were 23.7 and 0.77, respectively. The presence of anti-p62 was associated with higher levels of bilirubin and alkaline phosphatase (P < 0.001). The odds ratio for survival was 2.44 (95% CI: 0.87-6.87; P=0.091).
CONCLUSIONS
Anti-p62 may be regarded as a significant serological marker of PBC.

Keyword

Nucleoporin p62; Primary biliary cholangitis; ELISA; Autoantibodies; Liver; Recombinant protein

MeSH Terms

Alkaline Phosphatase
Autoantibodies*
Bilirubin
Blood Donors
Cholangitis*
Cholangitis, Sclerosing
Enzyme-Linked Immunosorbent Assay
Hepatitis, Autoimmune
Humans
Liver
Liver Diseases
Nuclear Pore Complex Proteins*
Odds Ratio
Prevalence
Sensitivity and Specificity
Alkaline Phosphatase
Autoantibodies
Bilirubin
Nuclear Pore Complex Proteins

Figure

• 

  Fig. 1 Anti-nucleoporin p62 antibodies in sera of PBC patients (N=135) and controls (N=100; 30 AIH patients, 30 PSC patients, and 40 healthy controls).Abbreviations: anti-p62, anti-nucleoporin p62 antibodies; PBC, primary biliary cholangitis; AIH, autoimmune hepatitis; PSC, primary sclerosing cholangitis.

• 

  Fig. 2 ROC curve analysis for anti-p62 antibodies in PBC patients (N=135). Area under the ROC curve was 0.6830 (95% confidence interval, 0.5865–0.7352) with cut-off point of 10.5 U/mL.Abbreviations: anti-p62, anti-nucleoporin p62 antibodies; PBC, primary biliary cholangitis.

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