477 Bloch, et al: PBC and cytoplasmic autoantibodies The Cytoplasmic Dot Staining Pattern Is Detected in a Subgroup of Patients with Primary Biliary Cirrhosis DONALD B. BLOCH, JIANG HONG YU, WEI-HONG YANG, FIONA GRAEME-COOK, KEITH D. LINDOR, ANJALI VISWANATHAN, KENNETH D. BLOCH, and AYAKO NAKAJIMA ABSTRACT. Objective. To determine the clinical significance of the cytoplasmic dot anti-“nuclear” antibody (ANA) staining pattern. Methods. We describe a patient with fatigue, arthralgias, elevated serum transaminase, and antibod- ies staining 5–20 cytoplasmic dots in HEp-2 cells. A liver biopsy revealed the presence of Stage III primary biliary cirrhosis (PBC). Using 2-color immunofluorescence, we determined the relationship between the cytoplasmic dot staining pattern and that produced by antibodies directed against the GW182 component of mRNA processing bodies. To determine the prevalence of the cytoplasmic dot staining pattern in patients with PBC, sera from 493 patients were tested for antibodies producing this staining pattern. Results. Antibodies in our patient’s serum colocalized with anti-GW182 antibodies in cytoplasmic dots, but did not react with recombinant GW182, suggesting that they were directed against an addi- tional component(s) of these structures. The cytoplasmic dot staining pattern was observed in 21 of 493 (4.3%) patients with PBC. In comparison, this staining pattern was not produced by serum from 248 patients with other autoimmune diseases. Conclusion. A subset of patients with PBC have autoantibodies that produce the cytoplasmic dot staining pattern. These antibodies react with one or more as yet unidentified components of the mRNA processing body. Appreciation of the clinical significance of the cytoplasmic dot staining pat- tern may assist in appropriate diagnosis and treatment of patients with PBC. (J Rheumatol 2005; 32:477–83) Key Indexing Terms: ANTINUCLEAR ANTIBODIES PRIMARY BILIARY CIRRHOSIS CYTOPLASMIC AUTOANTIGENS From the Departments of Medicine and Pathology, Harvard Medical School, Boston, Massachusetts; the Center for Immunology and Inflammatory Diseases and the Cardiovascular Research Center of the General Medical Services, Massachusetts General Hospital, Boston, Massachusetts; and the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. Supported by grants from the Arthritis Foundation (DBB), the National Institutes of Health (DK-051179 to DBB, HL-57172 to KDB), and a pilot grant from the Harvard Clinical Nutrition Center (DK-40561). K.D. Bloch was supported by an Established Investigator Award and D.B. Bloch by an Established Investigator Grant from the American Heart Association. D.B. Bloch, MD, Assistant Professor of Medicine; J.H. Yu, MD, Research Fellow; W-H. Yang, MD, Research Fellow; F. Graeme-Cook, MB, BCh, Assistant Professor of Pathology; K.D. Bloch, MD, Associate Professor of Medicine; A. Nakajima, MD, Research Fellow, Harvard Medical School; K.D. Lindor, MD, Professor of Medicine, Mayo Clinic College of Medicine; A. Viswanathan, MD, Clinical Fellow, St. Vincent’s Catholic Medical Center, Staten Island, NY. Address reprint requests to Dr. D.B. Bloch, Massachusetts General Hospital-East, CNY 149 13th Street, Charlestown, MA 02129. E-mail: bloch@helix.mgh.harvard.edu Submitted April 26, 2004; revision accepted October 13, 2004. Autoantibodies directed against cellular components are present in the serum of patients with autoimmune diseases, and the ability to detect autoantibodies assists the diagnosis and treatment of these patients. Autoantibodies producing the “cytoplasmic dot” staining pattern react with 5–20 cir- cumscribed cytoplasmic structures. This staining pattern is rare and was detected by Garcia-Lozano, et al in approxi- mately 1 in 1000 serum samples submitted for testing for antinuclear antibodies (ANA) 1 . The cytoplasmic dot stain- ing pattern is distinct from other cytoplasmic staining pat- terns, including those produced by antibodies directed against Golgi apparatus, ribosomal P proteins, tRNA syn- thetases, mitochondria, and peroxisomes. Primary biliary cirrhosis (PBC) is characterized by the progressive destruction of intrahepatic biliary ductules (as reviewed 2 ). Identification of patients with PBC is critical because treatment with ursodeoxycholic acid (UDCA) improves survival free of liver failure 3 . Early in the course of PBC, patients may report fatigue and vague musculoskeletal pain. Because of these symptoms, patients frequently present to a general internist or rheumatologist for initial evaluation, which may include testing for the presence of ANA. These tests may show nuclear staining and/or cytoplasmic staining. We report that the cytoplasmic dot staining pattern was detected in a subgroup of patients with PBC. MATERIALS AND METHODS Data were compiled from the following sources: our own case, described below, serum samples from 2 groups of patients with PBC (cohorts from Toronto, Ontario, Canada, and Mayo Clinic, Rochester, Minnesota, USA), and serum samples from 248 patients with other autoimmune diseases seen at the Massachusetts General Hospital, Boston, Massachusetts, USA. Personal non-commercial use only. The Journal of Rheumatology Copyright © 2005. All rights reserved. www.jrheum.org Downloaded on June 19, 2022 from