Markel Gal, Imazio Massimo, Koren-Morag Nira, Galore-Haskel Gilli, Schachter Jacob, Besser Michal, Cumetti Davide, Maestroni Silvia, Altman Arie, Shoenfeld Yehuda, Brucato Antonio, Adler Yehuda
Ella Lemelbaum Institute of Melanoma, Sheba Medical Center, Tel Hashomer, Israel.
Talpiot Medical Leadership Program, Sheba Medical Center, Tel Hashomer, Israel.
Oncotarget. 2016 Apr 5;7(14):17885-95. doi: 10.18632/oncotarget.7530.
The immune response plays a significant role in pericarditis, but the mechanisms of disease are poorly defined. Further, efficient monitoring and predictive clinical tools are unavailable. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an immune-inhibitory protein, while MHC class I chain related protein A (MICA) and B (MICB) have an immune-stimulating function.
Serum CEACAM1, MICA and MICB concentrations were measured by ELISA in ~50 subjects of each group: acute pericarditis (AP), recurrent pericarditis (RP) and lupus (SLE) patients, metastatic melanoma patients as well as healthy donors. Serum CEACAM1 was dramatically elevated in AP and RP patients, but not in SLE patients, and displayed a highly accurate profile in ROC curve analyses. MICA and MICB were elevated in some pericarditis patients. All markers were enhanced in metastatic melanoma patients irrespective of neoplastic pericardial involvement. Etiology-guided analysis of RP patients showed that very low MICA levels were associated with idiopathic RP, while high MICA was associated with autoimmune and post-operative RP. Importantly, MICA was significantly associated with recurrences, independently of other potentially confounding parameters such as age, time of follow up or treatment modality.
Here we report for the first time on CEACAM1 as a potentially novel biomarker for pericarditis, as well as on MICA as an innovative prognostic marker in these patients. Determination of the roles of these immune factors, as well as their diagnostic and prognostic values should be determined in future prospective studies.
免疫反应在心包炎中起重要作用,但疾病机制尚不明确。此外,目前尚无有效的监测和预测临床工具。癌胚抗原细胞粘附分子1(CEACAM1)是一种免疫抑制蛋白,而MHC I类链相关蛋白A(MICA)和B(MICB)具有免疫刺激功能。
通过酶联免疫吸附测定法(ELISA)测量了每组约50名受试者的血清CEACAM1、MICA和MICB浓度,这些受试者包括急性心包炎(AP)患者、复发性心包炎(RP)患者、狼疮(SLE)患者、转移性黑色素瘤患者以及健康供体。AP和RP患者的血清CEACAM1显著升高,但SLE患者未升高,并且在ROC曲线分析中显示出高度准确的特征。一些心包炎患者的MICA和MICB升高。无论是否有肿瘤性心包受累,转移性黑色素瘤患者的所有标志物均升高。对RP患者进行病因导向分析显示,极低的MICA水平与特发性RP相关,而高MICA与自身免疫性和术后RP相关。重要的是,MICA与复发显著相关,独立于其他潜在的混杂参数,如年龄、随访时间或治疗方式。
我们首次报道CEACAM1作为心包炎一种潜在的新型生物标志物,以及MICA作为这些患者的一种创新预后标志物。这些免疫因子的作用及其诊断和预后价值应在未来的前瞻性研究中确定。