title: Overcoming a "probable" diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature.
abstract: 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.
authors.affiliation: Laboratorio di Patologia Clinica, Ospedale Civile, Tolmezzo, Italy. nicola.bizzaro@ass3.sanita.fvg.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Bizzaro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Covini
authors.forename: Floriano
authors.initials: F
authors.lastname: Rosina
authors.forename: Paolo
authors.initials: P
authors.lastname: Muratori
authors.forename: Elio
authors.initials: E
authors.lastname: Tonutti
authors.forename: Danilo
authors.initials: D
authors.lastname: Villalta
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Pesente
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Alessio
authors.forename: Marilina
authors.initials: M
authors.lastname: Tampoia
authors.forename: Antonio
authors.initials: A
authors.lastname: Antico
authors.forename: Stefan
authors.initials: S
authors.lastname: Platzgummer
authors.forename: Brunetta
authors.initials: B
authors.lastname: Porcelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Terzuoli
authors.forename: Marco
authors.initials: M
authors.lastname: Liguori
authors.forename: Danila
authors.initials: D
authors.lastname: Bassetti
authors.forename: Ignazio
authors.initials: I
authors.lastname: Brusca
authors.forename: Piero L
authors.initials: PL
authors.lastname: Almasio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tarantino
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonaguri
authors.forename: Paolo
authors.initials: P
authors.lastname: Agostinis
authors.forename: Elena
authors.initials: E
authors.lastname: Bredi
authors.forename: Renato
authors.initials: R
authors.lastname: Tozzoli
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.forename: Carlo
authors.initials: C
authors.lastname: Selmi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology*
chemical_list: D001323:Autoantibodies