Banjara Manoj, Ghosh Chaitali, Dadas Aaron, Mazzone Peter, Janigro Damir
Cerebrovascular Research, Cleveland Clinic Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America.
Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America.
PLoS One. 2017 Jul 26;12(7):e0181409. doi: 10.1371/journal.pone.0181409. eCollection 2017.
Antibodies against brain proteins were identified in the plasma of cancer patients and are defined to cause paraneoplastic neurological syndromes. The profiles of brain-directed antibodies in non-small cell lung cancer (NSCLC) are largely unknown. Here, for the first time, we compared autoantibodies against brain proteins in NSCLC (n = 18) against those present in age-matched non-cancer control subjects (n = 18) with a similar life-style, habit, and medical history. Self-recognizing immunoglobulin (IgG) are primarily directed against cells in the cortex (P = 0.008), hippocampus (P = 0.003-0.05), and cerebellum (P = 0.02). More specifically, IgG targets were prominent in the pyramidal, Purkinje, and granule cell layers. Furthermore, autoimmune IgG signals were localized to neurons (81%), astrocytes (48%), and endothelial (29%) cells. While cancer sera yielded overall higher intensity signals, autoantigens of 100, 65, 45, 37, and 30 kDa molecular weights were the most represented. Additionally, a group of 100 kDa proteins seem more prevalent in female adenocarcinoma patients (4/5, 80%). In conclusion, our results revealed autoantigen specificity in NSCLC, which implicitly depends on patient's demographics and disease history. Patients at risk for lung cancer but with no active disease revealed that the immune profile in NSCLC is disease-dependent.
在癌症患者的血浆中发现了针对脑蛋白的抗体，这些抗体被认为会引发副肿瘤性神经综合征。非小细胞肺癌（NSCLC）中脑靶向抗体的情况在很大程度上尚不明确。在此，我们首次将18例NSCLC患者的脑蛋白自身抗体与年龄匹配、生活方式、习惯和病史相似的18例非癌症对照受试者的脑蛋白自身抗体进行了比较。自身识别免疫球蛋白（IgG）主要针对皮质（P = 0.008）、海马体（P = 0.003 - 0.05）和小脑（P = 0.02）中的细胞。更具体地说，IgG靶点在锥体细胞层、浦肯野细胞层和颗粒细胞层中较为突出。此外，自身免疫性IgG信号定位于神经元（81%）、星形胶质细胞（48%）和内皮细胞（29%）。虽然癌症血清产生总体强度更高的信号，但分子量为100、65、45、37和30 kDa的自身抗原最为常见。此外，一组100 kDa的蛋白似乎在女性腺癌患者中更为普遍（4/5，80%）。总之，我们的结果揭示了NSCLC中的自身抗原特异性，这隐含地取决于患者的人口统计学特征和疾病史。有肺癌风险但无活动性疾病的患者表明，NSCLC中的免疫特征与疾病相关。
