PML nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis.

Some patients with primary biliary cirrhosis (PBC) have antinuclear antibodies (ANAs). These ANAs include the “ multiple nuclear dots ” (MND) staining pattern, targeting promyelocytic leukemia protein (PML) nuclear body (NB) components, such as “ speckled 100-kD ” protein (Sp100) and PML. A new PML NB protein, designated as Sp140, was identifi ed using serum from a PBC patient. The aim of this study was to analyze the immune response against Sp140 protein in PBC patients. METHODS: We studied 135 PBC patients and 157 pathological controls with type 1 autoimmune hepatitis, primary sclerosing cholangitis, and systemic lupus erythematosus. We used indirect immunofl uorescence and a neuroblastoma cell line expressing Sp140 for detecting anti-Sp140 antibodies, and a commercially available immunoblot for detecting anti-Sp100 and anti-PML antibodies. RESULTS: Anti-Sp140 antibodies were present in 20 (15 % ) PBC patients but not in control samples, with a higher frequency in antimitochondrial antibody (AMA)-negative cases (53 vs. 9 % , P < 0.0001). Anti-Sp140 antibodies were found together with anti-Sp100 antibodies in all but one case (19 of 20, 90 % ) and with anti-PML antibodies in 12 (60 % ) cases. Anti-Sp140 positivity was not associated with a specifi c clinical feature of PBC. CONCLUSIONS: Our study identifi es Sp140 as a new, highly specifi c autoantigen in PBC for the fi rst time. The very frequent coexistence of anti-Sp140, anti-Sp100 and anti-PML antibodies suggests that the NB is a multiantigenic complex in PBC and enhances the diagnostic signifi cance of these reactivities, which are particularly useful in AMA-negative cases.