Overcoming a "Probable" diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: Study of 100 sera and review of the literature

Nicola Bizzaro, Giovanni Covini, Floriano Rosina, Paolo Muratori, Elio Tonutti, Danilo Villalta, Fiorenza Pesente, Maria Grazia Alessio, Marilina Tampoia, Antonio Antico, Stefan Platzgummer, Brunetta Porcelli, Lucia Terzuoli, Marco Liguori, Danila Bassetti, Ignazio Brusca, Piero L. Almasio, Giuseppe Tarantino, Chiara Bonaguri, Paolo AgostinisElena Bredi, Renato Tozzoli, Pietro Invernizzi, Carlo Selmi

Research output: Contribution to journalArticlepeer-review


Serum anti-mitochondrial antibodies (AMA) are the serological hallmark of primary biliary cirrhosis (PBC), yet up to 15% of PBC sera are AMA negative at routine indirect immunofluorescence (IIF) while being referred to as "probable" cases. The diagnostic role of PBC-specific antinuclear antibodies (ANA) remains to be determined. We will report herein data on the accuracy of new laboratory tools for AMA and PBC-specific ANA in a large series of PBC sera that were AMA-negative at IIF. We will also provide a discussion of the history and current status of AMA detection methods. We included IIF AMA-negative PBC sera (n=100) and sera from patients with other chronic liver diseases (n=104) that had been independently tested for IIF AMA and ANA; sera were blindly tested with an ELISA PBC screening test including two ANA (gp210, sp100) and a triple (pMIT3) AMA recombinant antigens. Among IIF AMA-negative sera, 43/100 (43%) manifested reactivity using the PBC screening test. The same test was positive for 6/104 (5.8%) control sera. IIF AMA-negative/PBC screen-positive sera reacted against pMIT3 (11/43), gp210 (8/43), Sp100 (17/43), both pMIT3 and gp210 (1/43), or both pMIT3 and Sp100 (6/43). Concordance rates between the ANA pattern on HEp-2 cells and specific Sp100 and gp210 ELISA results in AMA-negative subjects were 92% for nuclear dots and Sp100 and 99% for nuclear rim and gp210. Our data confirm the hypothesis that a substantial part of IIF AMA-negative (formerly coined "probable") PBC cases manifest disease-specific autoantibodies when tested using newly available tools and thus overcome the previously suggested diagnostic classification. As suggested by the recent literature, we are convinced that the proportion of AMA-negative PBC cases will be significantly minimized by the use of new laboratory methods and recombinant antigens.

Original languageEnglish
Pages (from-to)288-297
Number of pages10
JournalClinical Reviews in Allergy and Immunology
Issue number3
Publication statusPublished - Jun 2012


  • Autoimmune cholangitis
  • Diagnostic accuracy
  • Nuclear dots
  • Recombinant antigens
  • Rim like

ASJC Scopus subject areas

  • Immunology and Allergy


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