The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: a review of literature
Abstract
Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an autoimmune disease of the liver characterized by anti-mitochondrial antibodies (AMA) in 90%–95% of patients. The aim of this study was to evaluate the diagnostic value of several serum biomarkers in patients with PBC but negative for AMA. Some antinuclear antibodies (ANA) pattern, detected by indirect immunofluorescence (IIF), such as multiple nuclear dot (MND) and rim-like patterns are well-known to be specific for PBC. The corresponding nuclear antigens are the components of the nuclear pore complex (Gp210 for rim-like pattern) and Sp100, PML proteins (for MND pattern) detectable by immunoblotting and ELISA methods. More recently, new biomarkers have been evaluated in order to improve the diagnostic sensitivity, such as kelch-like 12 (KLHL12) and hexokinase-1. Considering these different serum biomarkers, studies evaluating their diagnostic role in AMA-negative PBC patients compared to AMA-positive ones and controls were included in this review. Pooled sensitivity and specificity were 37% and 85%, respectively. The overall PPV and NPV mean values were 45% and 83%. Even if all biomarkers are very specific for PBC, the overall sensitivity was poor and therefore is necessary to identify a marker with a greater sensitivity for PBC in AMA-negative patients.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Leuschner U. Primary biliary cirrhosis – presentation and diagnosis. Clin Liver Dis 2003;7:741–58.10.1016/S1089-3261(03)00101-6Suche in Google Scholar
2. Granito A, Yang WH, Muratori L, Lim MJ, Nakajima A, Ferri S, et al. PML nuclear body component sp140 is a novel autoantigen in primary biliary cirrhosis. Am J Gastroenterol 2010;105:125–31.10.1038/ajg.2009.596Suche in Google Scholar PubMed
3. Liu B, Shi XH, Zhang FC, Zhang W, Gao LX. Antimitochondrial antibody-negative primary biliary cirrhosis: a subset of primary biliary cirrhosis. Liver Int 2008;28:233–9.10.1111/j.1478-3231.2007.01651.xSuche in Google Scholar PubMed
4. Gao L, Tian X, Liu B, Zhang F. The value of antinuclear antibodies in primary biliary cirrhosis. Clin Exp Med 2008;8:9–15.10.1007/s10238-008-0150-6Suche in Google Scholar PubMed
5. Granito A, Muratori P, Muratori L, Pappas G, Cassani F, Worthington J, et al. Antinuclear antibodies giving the ‘multiple nuclear dots’ or the ‘rim-like/membranous’ patterns: diagnostic accuracy for primary biliary cirrhosis. Aliment Pharmacol Ther 2006;24:1575–83.10.1111/j.1365-2036.2006.03172.xSuche in Google Scholar PubMed
6. Ueno Y, Ishii M, Takahashi S, Mano Y, Yahagi K, Kisara N, et al. Primary biliary cirrhosis with antibody against carbonic anhydrase II associates with distinct immunological backgrounds. Hepatol Res 2001;20:18–27.10.1016/S1386-6346(00)00128-5Suche in Google Scholar PubMed
7. Muratori P, Muratori L, Lenzi M, Bianchi FB. Antibodies to carbonic anhydrase in autoimmune cholangiopathy. Gastroenterolgy 1997;112:1053–4.10.1053/gast.1997.v112.agast971053Suche in Google Scholar PubMed
8. Gordon SC, Quattrociocchi-Longe TM, Khan BA, Kodali VP, Chen J, Silverman AL, et al. Antibodies to carbonic anhydrase in patients with immune cholangiopathies. Gastroenterology 1995;108:1802–9.10.1016/0016-5085(95)90143-4Suche in Google Scholar PubMed
9. Norman GL, Yang CY, Ostendorff HP, Shums Z, Lim MJ, Wang J, et al. Anti-kelch-like 12 and anti-hexokinase 1: novel autoantibodies in primary biliary cirrhosis. Liver Int 2015;35:642–51.10.1111/liv.12690Suche in Google Scholar PubMed PubMed Central
10. Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097.10.1371/journal.pmed.1000097Suche in Google Scholar PubMed PubMed Central
11. Heathcote EJ. Management of primary biliary cirrhosis. The American Association for the study of liver disease practice guidelines. Hepatology 2000;31:1005–13.10.1053/he.2000.5984Suche in Google Scholar PubMed
12. Rigopoulou EI, Davies ET, Pares A, Zachou K, Liaskos C, Bogdanos DP, et al. Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis. Gut 2005;54:528–32.10.1136/gut.2003.036558Suche in Google Scholar PubMed PubMed Central
13. Muratori P, Muratori L, Ferrari R, Cassani F, Bianchi G, Lenzi M, et al. Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am J Gastroenterol 2003;98:431–7.10.1111/j.1572-0241.2003.07257.xSuche in Google Scholar PubMed
14. Invernizzi P, Crosignani A, Battezzati PM, Covini G, De Valle G, Larghi A, et al. Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis. Hepatology 1997;25:1090–5.10.1002/hep.510250507Suche in Google Scholar PubMed
15. Comay D, Cauch-Dudek K, Hemphill D, Diamandis E, Wanless I, Heathcote EJ. Are antibodies to carbonic anhydrase II specific for anti-mitochondrial antibody-negative primary biliary cirrhosis? Dig Dis Sci 2000;45:2018–21.10.1023/A:1005548126211Suche in Google Scholar
16. Invernizzi P, Battezzati PM, Crosignani A, Zermiani P, Bignotto M, Del Papa N, et al. Antibody to carbonic anhydrase II is present in primary biliary cirrhosis (PBC) irrespective of antimitochondrial antibody status. Clin Exp Immunol 1998;114:448–54.10.1046/j.1365-2249.1998.00735.xSuche in Google Scholar PubMed PubMed Central
17. Bizzaro N, Covini G, Rosina F, Muratori P, Tonutti E, Villalta D, et al. Overcoming a “portable” diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature. Clin Rev Allergy Immunol 2012;42:288–97.10.1007/s12016-010-8234-ySuche in Google Scholar PubMed
©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Method comparison – a practical approach based on error identification
- Review
- Neutrophil gelatinase-associated lipocalin as a risk marker in cardiovascular disease
- Mini Reviews
- α-Defensin point-of-care test for diagnosis of prosthetic joint infections: neglected role of laboratory and clinical pathologists
- The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: a review of literature
- Opinion Paper
- New issues on measurement of B-type natriuretic peptides
- Genetics and Molecular Diagnostics
- The SEeMORE strategy: single-tube electrophoresis analysis-based genotyping to detect monogenic diseases rapidly and effectively from conception until birth
- General Clinical Chemistry and Laboratory Medicine
- Determination of serum calcium levels by 42Ca isotope dilution inductively coupled plasma mass spectrometry
- The effects of dry ice exposure on plasma pH and coagulation analyses
- Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia
- Circulating CD89-IgA complex does not predict deterioration of kidney function in Korean patients with IgA nephropathy
- Performance analysis of automated evaluation of Crithidia luciliae-based indirect immunofluorescence tests in a routine setting – strengths and weaknesses
- Performance of automated digital cell imaging analyzer Sysmex DI-60
- Reference Values and Biological Variations
- Determination of reference intervals for urinary steroid profiling using a newly validated GC-MS/MS method
- Reference intervals and longitudinal changes in copeptin and MR-proADM concentrations during pregnancy
- Definition of the upper reference limit of glycated albumin in blood donors from Italy
- Reference values of fecal calgranulin C (S100A12) in school aged children and adolescents
- Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose
- Cancer Diagnostics
- Cancer sniffer dogs: how can we translate this peculiarity in laboratory medicine? Results of a pilot study on gastrointestinal cancers
- Cardiovascular Diseases
- NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis
- Analytical evaluation of the new Beckman Coulter Access high sensitivity cardiac troponin I immunoassay
- Infectious Diseases
- Analytical evaluation of the performances of Diazyme and BRAHMS procalcitonin applied to Roche Cobas in comparison with BRAHMS PCT-sensitive Kryptor
- Effects of procalcitonin testing on antibiotic use and clinical outcomes in patients with upper respiratory tract infections. An individual patient data meta-analysis
- Acknowledgment
- Letters to the Editor
- Handling the altered test results of hemolyzed samples. Recommendations of the Quality, Management, Safety and Evidence Committee (CCGSE) of the Spanish Association of Medical Biopathology and Laboratory Medicine (AEBM-ML)
- Reply to: Analytical evaluation of the performances of Diazyme and BRAHMS procalcitonin applied to Roche Cobas in comparison with BRAHMS PCT-sensitive Kryptor
- Excessive hypercortisolemia due to ectopic Cushing’s syndrome requiring extending the reportable range for plasma cortisol for management
- Heavy chain disease: our experience
- An abnormal elevation of serum CA72-4 due to taking colchicine
- Rivaroxaban non-responders: do plasma measurements have a place?
- Next generation sequencing and immuno-histochemistry profiling identify numerous biomarkers for personalized therapy of endometrioid endometrial carcinoma
- A multicenter effort to improve comparability of vitamin B6 assays in whole blood
- PR3-anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis
Artikel in diesem Heft
- Frontmatter
- Editorial
- Method comparison – a practical approach based on error identification
- Review
- Neutrophil gelatinase-associated lipocalin as a risk marker in cardiovascular disease
- Mini Reviews
- α-Defensin point-of-care test for diagnosis of prosthetic joint infections: neglected role of laboratory and clinical pathologists
- The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: a review of literature
- Opinion Paper
- New issues on measurement of B-type natriuretic peptides
- Genetics and Molecular Diagnostics
- The SEeMORE strategy: single-tube electrophoresis analysis-based genotyping to detect monogenic diseases rapidly and effectively from conception until birth
- General Clinical Chemistry and Laboratory Medicine
- Determination of serum calcium levels by 42Ca isotope dilution inductively coupled plasma mass spectrometry
- The effects of dry ice exposure on plasma pH and coagulation analyses
- Placental protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia
- Circulating CD89-IgA complex does not predict deterioration of kidney function in Korean patients with IgA nephropathy
- Performance analysis of automated evaluation of Crithidia luciliae-based indirect immunofluorescence tests in a routine setting – strengths and weaknesses
- Performance of automated digital cell imaging analyzer Sysmex DI-60
- Reference Values and Biological Variations
- Determination of reference intervals for urinary steroid profiling using a newly validated GC-MS/MS method
- Reference intervals and longitudinal changes in copeptin and MR-proADM concentrations during pregnancy
- Definition of the upper reference limit of glycated albumin in blood donors from Italy
- Reference values of fecal calgranulin C (S100A12) in school aged children and adolescents
- Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose
- Cancer Diagnostics
- Cancer sniffer dogs: how can we translate this peculiarity in laboratory medicine? Results of a pilot study on gastrointestinal cancers
- Cardiovascular Diseases
- NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis
- Analytical evaluation of the new Beckman Coulter Access high sensitivity cardiac troponin I immunoassay
- Infectious Diseases
- Analytical evaluation of the performances of Diazyme and BRAHMS procalcitonin applied to Roche Cobas in comparison with BRAHMS PCT-sensitive Kryptor
- Effects of procalcitonin testing on antibiotic use and clinical outcomes in patients with upper respiratory tract infections. An individual patient data meta-analysis
- Acknowledgment
- Letters to the Editor
- Handling the altered test results of hemolyzed samples. Recommendations of the Quality, Management, Safety and Evidence Committee (CCGSE) of the Spanish Association of Medical Biopathology and Laboratory Medicine (AEBM-ML)
- Reply to: Analytical evaluation of the performances of Diazyme and BRAHMS procalcitonin applied to Roche Cobas in comparison with BRAHMS PCT-sensitive Kryptor
- Excessive hypercortisolemia due to ectopic Cushing’s syndrome requiring extending the reportable range for plasma cortisol for management
- Heavy chain disease: our experience
- An abnormal elevation of serum CA72-4 due to taking colchicine
- Rivaroxaban non-responders: do plasma measurements have a place?
- Next generation sequencing and immuno-histochemistry profiling identify numerous biomarkers for personalized therapy of endometrioid endometrial carcinoma
- A multicenter effort to improve comparability of vitamin B6 assays in whole blood
- PR3-anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis