Similar T-Cell Oligoclonality in Antimitochondrial Antibody-Positive and -Negative Primary Biliary Cirrhosis MARLYN J. MAYO, MD, PETER E. LIPSKY, MD, SHARON N. MILLER, PhD, PETER STASTNY, MD, and BURTON COMBES, MD Approximately 5% of patients with clinical and histological features suggestive of primary biliary cirrhosis do not have anti-mitochondrial antibodies that can be detected by current methodologies. Although the role of these autoantibodies in the pathogenesis of liver disease is uncertain, T lymphocytes within the portal tracts are felt to be important mediators of bile duct destruction. In order to investigate the hypothesis that a similar T-cell process may be involved in both antimitochondrial antibody-positive and -negative primary biliary cirrhosis, we characterized the oligoclonally expanded T cells in both types of patients by analysis of complementarity determining region 3 length in peripheral blood mononuclear cells. The distribution of oligoclonally expanded T cells was similar in both groups. This finding does not support a distinct T-cell-mediated pathogenesis for anti-mitochondrial antibody-positive and -negative primary biliary cirrhosis but rather suggests that similar processes may be involved in the immunopathogenesis of both. KEY WORDS: autoimmunity; cholangitis; cholangiopathy; liver. Serum anti-mitochondrial antibodies (AMA) are present in 88 –97% of patients with primary biliary cirrhosis (PBC) (1). The ability to detect AMA can be increased by repeating the indirect immunofluores- cence test (2) or by performing immunoblotting for antibodies to the target mitochondrial antigens (3). However, approximately 3– 6% of patients with clin- ical, biochemical, and histological features compati- ble with PBC do not have detectable AMA by any of these methods. AMA-negative PBC patients have a similar clinical course, response to therapy with ursodeoxycholic acid, and outcome after liver transplantation as AMA-positive PBC patients (4 – 7). However, they have been noted to differ from AMA-positive PBC patients with respect to produc- tion of other antibodies, manifesting higher titers of anti-nuclear antibodies and lower total levels of IgM. Based on these differences, some have considered AMA-negative PBC to be a distinct entity, and the terms immunocholangitis, autoimmune cholangitis (8 –10), and autoimmune cholangiopathy (11) have been suggested. Whether this disparate antibody re- sponse is indicative of a unique pathogenesis or is just reflective of individual diversity of humoral immune Manuscript received February 15, 2000; accepted August 2, 2000. From the Department of Internal Medicine, Divisions of Hepa- tology, Rheumatic Diseases, and Transplant Immunology, Univer- sity of Texas Southwestern Medical Center at Dallas, Dallas, Texas. Dr. Mayo was the recipient of a NIH General Clinical Research Center Clinical Associate Physician Award. These studies were supported in part by an NIH General Clinical Research Center Grant to UT Southwestern (M)1-RR00633), by NIH grant (R01-DK46602), the Simmons Arthritis Research Cen- ter, and a research grant from Ciba Geigy. Preliminary results of this work were presented at the Annual Meeting of the American Association for the Study of Liver Dis- eases, November 1997, and published in abstract from (Hepatology 1997;26:439A) Address for reprint requests: Dr. Marlyn J. Mayo, Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75390-9151. Digestive Diseases and Sciences, Vol. 46, No. 2 (February 2001), pp. 345–351 345 Digestive Diseases and Sciences, Vol. 46, No. 2 (February 2001) 0163-2116/01/0200-0345$19.50/0 © 2001 Plenum Publishing Corporation