PML Nuclear Body Component Sp140 Is a Novel Autoantigen in... : Official journal of the American College of Gastroenterology | ACG (original) (raw)

ORIGINAL CONTRIBUTIONS: LIVER AND BILIARY TRACT

PML Nuclear Body Component Sp140 Is a Novel Autoantigen in Primary Biliary Cirrhosis

Granito, Alessandro MD1,5; Yang, Wei-Hong MD2,5; Muratori, Luigi MD, PhD1; Lim, Mark J PhD3; Nakajima, Ayako MD4; Ferri, Silvia MD1; Pappas, Georgios MD1; Quarneti, Chiara MD1; Bianchi, Francesco B MD1; Bloch, Donald B MD2,6; Muratori, Paolo MD1,6

1Dipartimento di Medicina Clinica, Alma Mater Studiorum University of Bologna, Bologna, Italy

2Department of Medicine, Harvard Medical School, Boston, Massachusetts, The Center for Immunology and Inflammatory Diseases of the General Medical Services, Massachusetts General Hospital, Boston, Massachusetts, USA

3AmberGen Inc., Watertown, Massachusetts, USA

4Institute of Rheumatology, Tokyo Women's Medical College, Tokyo, Japan

Correspondence: Alessandro Granito, MD, Dipartimento di Medicina Clinica, Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Hospital, Padiglione 11, Via Massarenti 9, 40138, Bologna, Italy. E-mail: [email protected]

5These authors contributed equally to this work and share first authorship

6These two authors contributed equally to this work.

published online 27 October 2009

Received 3 March 2009; accepted 11 September 2009

Abstract

OBJECTIVES:

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 identified 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 immunofluorescence 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 specific clinical feature of PBC.

CONCLUSIONS:

Our study identifies Sp140 as a new, highly specific autoantigen in PBC for the first 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 significance of these reactivities, which are particularly useful in AMA-negative cases.