Kobold Sebastian, Tams Sinje, Luetkens Tim, Cao Yanran, Sezer Orhan, Bartels Britta Marlen, Reinhard Henrike, Templin Julia, Bartels Katrin, Hildebrandt York, Lajmi Nesrine, Marx Andreas, Haag Friedrich, Bokemeyer Carsten, Kröger Nicolaus, Atanackovic Djordje
Department of Internal Medicine II, Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Clin Dev Immunol. 2011;2011:302145. doi: 10.1155/2011/302145. Epub 2011 Nov 15.
The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS). However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM). Screening 1094 peripheral blood (PB) sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2(211-230) as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients' BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT). Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n = 74). Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.
SOX2特异性自身抗体的出现似乎与意义未明的单克隆丙种球蛋白病（MGUS）患者预后改善相关。然而，尚不清楚在确诊的多发性骨髓瘤（MM）患者中是否也会产生SOX2特异性抗体。我们对196例MM患者的1094份外周血（PB）血清和100份健康供者的PB血清进行筛查，分别在7.7%的患者和2.0%的供者中检测到SOX2特异性自身抗体。我们确定SOX2(211 - 230)为完整蛋白序列中的免疫显性抗体表位。SOX2抗原在大多数健康组织中表达，其表达与骨髓驻留浆细胞数量无关。因此，抗SOX2免疫与患者骨髓中SOX2表达水平或肿瘤负荷无关。预测抗SOX2免疫发生的唯一临床因素是同种异体干细胞移植（alloSCT）的应用。接受alloSCT的患者（n = 74）中抗SOX2抗体出现得更频繁。此外，大多数SOX2血清阳性患者仅在alloSCT后才产生抗体。这一发现表明alloSCT能够打破对这种普遍表达抗原的耐受性。SOX2特异性自身抗体是否仅仅是一种附带现象、与移植物抗宿主效应有关还是参与骨髓瘤的免疫控制等问题，需要在前瞻性研究中予以解答。
