Differential epitope mapping of antibodies to PDC-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis.
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.
Bellucci
Roberto
R
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Oertelt
Sabine
S
Gallagher
Meagan
M
Li
Sigui
S
Zorn
Emmanuel
E
Weller
Edie
E
Porcheray
Fabrice
F
Alyea
Edwin P
EP
Soiffer
Robert J
RJ
Munshi
Nikhil C
NC
Gershwin
M Eric
ME
Ritz
Jerome
J
D000368:Aged; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D045744:Cell Line, Tumor; D051047:Dihydrolipoyllysine-Residue Acetyltransferase / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D006262:Health; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology* / Q000601:surgery*; D014184:Transplantation, Homologous / Q000276:immunology
D000906:Antibodies; D024101:Mitochondrial Proteins; D051047:Dihydrolipoyllysine-Residue Acetyltransferase