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Molecular diagnostics of primary biliary cirrhosis.

AbstractBACKGROUND:
Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology characterized by the presence of antimitochondrial antibodies (AMA) in 90 - 95% of patients. AMA are directed against members of 2-oxo-acid dehydrogenase complex, including mainly the E2 subunit of pyruvate dehydrogenase, the E2 subunit of branched chain 2-oxo-acid dehydrogenase complex and the E2 subunit of the oxoglutarate dehydrogenase complex. Apart from AMA, PBC is characterized by the presence of PBC-specific antinuclear antibodies (ANA). The molecular targets of these PBC-specific ANA have been characterized as gp210, lamin B receptor, nucleoporin 62, sp100 and promyelocytic leukemia proteins.
OBJECTIVE:
To discuss the molecular diagnostics of PBC in the context of AMA and PBC-specific ANA detection by the use of conventional and 'new' novel technologies.
METHODS:
Critical analysis of all published data regarding PBC serology between 1985 and 2007 was performed in order to suggest a diagnostic algorithm for the serological diagnosis of PBC.
RESULTS/CONCLUSIONS:
AMA are first detected by indirect immunofluorescence (IIF) on frozen sections of rat liver, kidney and stomach substrates. However, because IIF is time-consuming, labor-intensive and observer-dependent, molecular-based assays such as immunoblot and enzyme-linked immunosorbent assays have been developed with high sensitivity and specificity. Similarly, molecular-based assays have also been developed for the detection of PBC-specific ANA. The latter investigation seems to be of outmost importance because these autoantibodies can be used as a positive tool in the diagnosis of AMA-negative PBC while at the same time identifying a subgroup of PBC patients with more advanced disease. New test systems for the detection of PBC-specific antibodies based on the xMultiple Analyte Profiling Luminex methodology seems to be the future in molecular diagnostics of PBC as it was expected first to decrease the cost and second to speed up an accurate serological profile, although they may decrease further the proportion of AMA-negative PBC cases.
AuthorsEirini I Rigopoulou, George N Dalekos
JournalExpert opinion on medical diagnostics (Expert Opin Med Diagn) Vol. 2 Issue 6 Pg. 621-34 (Jun 2008) ISSN: 1753-0059 [Print] England
PMID23495774 (Publication Type: Journal Article)

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