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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. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-030304v1 109/5/2001    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bellucci, R. Articles by Ritz, J. Search for Related Content PubMed PubMed Citation Articles by Bellucci, R. Articles by Ritz, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 22, 2006 Accepted October 19, 2006 Differential epitope mapping of antibodies to PDC-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis Roberto Bellucci, Sabine Oertelt, Meagan Gallagher, Sigui Li, Emmanuel Zorn, Edie Weller, Fabrice Porcheray, Edwin P Alyea, Robert J Soiffer, Nikhil C Munshi, M Eric Gershwin, and Jerome Ritz* Dept of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Dept of Rheumatology, Allergy & Clinical Immunology, University of California, Davis, CA, United States Dept of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, United States Dept of Medicine, Brigham & Women's Hospital, Boston, MA, United States Harvard Medical School, Boston, MA, United States * Corresponding author; email: jerome_ritz{at}dfci.harvard.edu. 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) that underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received donor lymphocyte infusions (DLI) after transplant. 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 two of 6 patients with chronic leukemias (33%) developed anti-PDC-E2 antibodies in association with DLI response; two of 12 (17%) patients in the MGUS pre-treatment 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 transplant patients are distinct from PBC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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