可溶性MICA作为多发性骨髓瘤患者总生存期和无进展生存期的独立预后因素。

Soluble MICA as an independent prognostic factor for the overall survival and progression-free survival of multiple myeloma patients.

作者信息

Rebmann Vera, Schütt Philipp, Brandhorst Dieter, Opalka Bertram, Moritz Thomas, Nowrousian Mohammad Reza, Grosse-Wilde Hans

机构信息

Institute of Immunology, University Hospital Essen, Germany.

出版信息

Clin Immunol. 2007 Apr;123(1):114-20. doi: 10.1016/j.clim.2006.11.007. Epub 2007 Jan 10.

DOI:10.1016/j.clim.2006.11.007

PMID:17218152

Abstract

Major histocompatibility complex class I-related chain A (MICA) molecules are frequently expressed in lymphoproliferative malignancies including multiple myeloma (MM). MICA activates NK cells and co-stimulates T cells by interaction with its immunoreceptor NKG2D. In contrast, soluble MICA (sMICA) molecules impair the functions of NKG2D(+) T and NK cells, which may facilitate tumor cell escape from immunosurveillance. Here, we analyzed the clinical relevance of sMICA in 97 MM patients. sMICA (mean+/-SEM pg/ml) was significantly increased (p<0.0001) in patients (429+/-20) compared to controls (230+/-20; N=43). Serial determination showed a strong correlation between increments of sMICA and paraprotein levels (r=0.543, p<0.0001, N=49). sMICA levels >305 pg/ml are associated with a poor overall (p=0.004) and progression-free survival (p=0.002). Multivariate analysis revealed sMICA as an independent predictive factor for overall (p=0.007) and progression-free survival (p=0.002). Thus, our results suggest sMICA as a potent prognostic marker in MM, which may be useful to identify risk patients.

摘要

主要组织相容性复合体I类相关链A（MICA）分子在包括多发性骨髓瘤（MM）在内的淋巴增殖性恶性肿瘤中经常表达。MICA通过与其免疫受体NKG2D相互作用激活自然杀伤（NK）细胞并共同刺激T细胞。相比之下，可溶性MICA（sMICA）分子会损害NKG2D+ T细胞和NK细胞的功能，这可能会促进肿瘤细胞逃避免疫监视。在此，我们分析了97例MM患者中sMICA的临床相关性。与对照组（230±20；N = 43）相比，患者组（429±20）的sMICA（平均±标准误，pg/ml）显著升高（p<0.0001）。连续测定显示sMICA的升高与副蛋白水平之间存在强相关性（r = 0.543，p<0.0001，N = 49）。sMICA水平>305 pg/ml与总体生存率低（p = 0.004）和无进展生存率低（p = 0.002）相关。多变量分析显示sMICA是总体生存率（p = 0.007）和无进展生存率（p = 0.002）的独立预测因素。因此，我们的结果表明sMICA是MM中一种有效的预后标志物，可能有助于识别高危患者。