Bellucci Roberto, Oertelt Sabine, Gallagher Meagan, Li Sigui, Zorn Emmanuel, Weller Edie, Porcheray Fabrice, Alyea Edwin P, Soiffer Robert J, Munshi Nikhil C, Gershwin M Eric, Ritz Jerome
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Blood. 2007 Mar 1;109(5):2001-7. doi: 10.1182/blood-2006-06-030304. Epub 2006 Oct 26.
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.
自身免疫性肝病原发性胆汁性肝硬化（PBC）的一个独特特征是存在针对丙酮酸脱氢酶复合物（PDC）E2成分的高滴度且极具特异性的自身抗体。仅在患有该疾病的患者或随后发展为PBC的患者中检测到针对PDC - E2抗原的自身抗体。一个例外是一组接受异基因造血干细胞移植（HSCT）并在移植后接受供体淋巴细胞输注（DLI）的多发性骨髓瘤（MM）患者。这些患者体内出现了针对多种骨髓瘤相关抗原（包括PDC - E2）的高滴度抗体，同时体内骨髓瘤细胞被排斥。为了研究这些患者中针对PDC的自身抗体的特异性，我们筛选了来自MM患者、慢性白血病患者、意义未明的单克隆丙种球蛋白病（MGUS）患者、PBC患者以及健康供体的血清。11例MM患者中有3例（27%）以及6例慢性白血病患者中有2例（33%）在DLI反应时出现了抗PDC - E2抗体；MGUS预处理对照组的12例患者中有2例（17%）也检测到了抗PDC反应。有趣的是，这些PDC - E2自身抗体的表位特异性是独特的，这表明导致移植患者免疫耐受丧失的机制与PBC不同。
