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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2001-2007.
Prepublished online as a Blood First Edition Paper on October 26, 2006; DOI 10.1182/blood-2006-06-030304.


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IMMUNOBIOLOGY

Differential epitope mapping of antibodies to PDC-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis

Roberto Bellucci1,2,3, Sabine Oertelt4, Meagan Gallagher1, Sigui Li5, Emmanuel Zorn1,2,3, Edie Weller5, Fabrice Porcheray1,2,3, Edwin P. Alyea1,2,3, Robert J. Soiffer1,2,3, Nikhil C. Munshi1,2,3, M. Eric Gershwin4, and Jerome Ritz1,2,3

1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; 2 Department of Medicine, Brigham and Woman's Hospital, Boston, MA; 3 Harvard Medical School, Boston, MA; 4 Department of Rheumatology, Allergy and Clinical Immunology, University of California, Davis; 5 Department of Biostatistics, Dana-Farber Cancer Institute, Boston, MA

A unique characteristic of the autoimmune liver disease primary biliary cirrhosis (PBC) is the presence of high-titer and extremely specific autoantibodies to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Autoantibodies to PDC-E2 antigen have only been detected in patients with disease or in those who subsequently develop PBC. One exception has been a subgroup of patients with multiple myeloma (MM) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received donor lymphocyte infusions (DLIs) after transplantation. These patients developed high-titer antibodies to a variety of myeloma-associated antigens, including PDC-E2, coincident with rejection of myeloma cells in vivo. To examine the specificity of autoantibodies to PDC in these patients, we screened sera from patients with MM, chronic leukemias, monoclonal gammopathy of unknown significance (MGUS), PBC, and healthy donors. Three of 11 patients with MM (27%) and 2 of 6 patients with chronic leukemias (33%) developed anti–PDC-E2 antibodies in association with DLI response; 2 of 12 (17%) patients in the MGUS pretreatment control population also had detectable anti-PDC responses. Interestingly, the epitope specificity of these PDC-E2 autoantibodies was distinctive, suggesting that the mechanisms leading to loss of tolerance in the transplantation patients are distinct from PBC.


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