白细胞介素-10（IL-10）-1082 单核苷酸多态性（SNP）与原发性中枢神经系统和眼内视网膜淋巴瘤。
IL-10 -1082 SNP and IL-10 in primary CNS and vitreoretinal lymphomas.
机构信息
Immunopathology Section, Laboratory of Immunology National Institutes of Health, 10 Center Drive, 10/10 N103, NIH/NEI, Bethesda, MD, 20892-1857, USA.
出版信息
Graefes Arch Clin Exp Ophthalmol. 2012 Oct;250(10):1541-8. doi: 10.1007/s00417-012-2037-1. Epub 2012 May 25.
OBJECTIVES
Most primary central nervous system lymphomas (PCNSLs) and primary vitreoretinal lymphomas (PVRLs) are B-cell lymphomas that produce high levels of interleukin (IL)-10, which is linked to rapid disease progression. The IL-10 (-1082) G → A polymorphism (IL-10 SNP) is associated with improved survival in certain non-CNS lymphoma patients. PDCD4 is a tumor suppressor gene and upstream regulator of IL-10. This study examined the correlation between the IL-10 SNP, PDCD4 mRNA expression, and IL-10 expression (at transcript and protein levels) in these lymphoma cells.
MATERIALS AND METHODS
Single-nucleotide polymorphism (SNP)-typing at IL-10 (-1082) was performed after microdissecting cytospun PVRL cells from 26 specimens. Vitreal IL-10 and IL-6 levels were measured by ELISA. PCNSL cells from 52 paraffin-embedded sections were microdissected and SNP typed on genomic DNA. RT-PCR was performed to analyze expression of IL-10 and PDCD4 mRNA. IL-10 (-1082) SNP typing was performed on blood samples of 96 healthy controls. We measured IL-10 (-1082) SNP expression in 26 PVRLs and 52 PCNSLs and examined its relationship with IL-10 protein and gene expression, respectively.
RESULTS
More PVRL patients expressed one copy of the IL-10 ( -1082 ) G → A SNP with the GA genotype compared to controls. The frequencies of the three genotypes (AA, AG, GG) significantly differed in PVRL versus controls and in PCNSL versus controls. In PVRLs, the vitreal IL-10/IL-6 ratio was higher in IL-10 (-1082) AG and IL-10 (-1082) AA patients, compared to IL-10 (-1082) GG patients. IL-10 mRNA expression was higher in IL-10 (-1082) AG and IL-10 (-1082) AA PCNSLs, compared to IL-10 (-1082) GG PCNSLs. No correlation was found between IL-10 and PDCD4 expression levels in 37 PCNSL samples.
CONCLUSIONS
PVRL and PCNSL patients had similar IL-10 (-1082) A allele frequencies, but genotype distributions differed from healthy controls. The findings suggest that the IL-10 (-1082) A allele is a risk factor for higher IL-10 levels in PVRLs and PCNSLs. Higher IL-10 levels have been correlated with more aggressive disease in both PVRLs and PCNSLs, making this finding an important and potentially clinically significant observation.
目的
大多数原发性中枢神经系统淋巴瘤（PCNSL）和原发性玻璃体视网膜淋巴瘤（PVRL）是产生高水平白细胞介素（IL）-10 的 B 细胞淋巴瘤，这与疾病的快速进展有关。IL-10（-1082）G→A 多态性（IL-10 SNP）与某些非中枢神经系统淋巴瘤患者的生存改善有关。PDCD4 是肿瘤抑制基因和 IL-10 的上游调节剂。本研究检测了这些淋巴瘤细胞中 IL-10 SNP、PDCD4 mRNA 表达和 IL-10 表达（转录和蛋白水平）之间的相关性。
材料和方法
对 26 个标本的细胞进行微切割后，对 IL-10（-1082）的单核苷酸多态性（SNP）进行分型。通过 ELISA 测量玻璃体 IL-10 和 IL-6 水平。对 52 个石蜡包埋切片中的 PCNSL 细胞进行微切割并对基因组 DNA 进行 SNP 分型。通过 RT-PCR 分析 IL-10 和 PDCD4 mRNA 的表达。对 96 名健康对照者的血液样本进行 IL-10（-1082）SNP 分型。我们对 26 个 PVRL 和 52 个 PCNSL 进行了 IL-10（-1082）SNP 表达的检测，并分别检测了其与 IL-10 蛋白和基因表达的关系。
结果
与对照组相比，更多的 PVRL 患者表达了 IL-10（-1082）G→A SNP 的一个拷贝，具有 GA 基因型。三种基因型（AA、AG、GG）在 PVRL 与对照组以及 PCNSL 与对照组之间的频率有显著差异。在 PVRL 中，与 IL-10（-1082）GG 患者相比，IL-10（-1082）AG 和 IL-10（-1082）AA 患者的玻璃体 IL-10/IL-6 比值更高。与 IL-10（-1082）GG PCNSL 相比，IL-10（-1082）AG 和 IL-10（-1082）AA PCNSL 中的 IL-10 mRNA 表达更高。在 37 个 PCNSL 样本中，未发现 IL-10 和 PDCD4 表达水平之间存在相关性。
结论
PVRL 和 PCNSL 患者具有相似的 IL-10（-1082）A 等位基因频率，但基因型分布与健康对照组不同。这些发现表明，IL-10（-1082）A 等位基因是 PVRL 和 PCNSL 中 IL-10 水平升高的危险因素。在 PVRL 和 PCNSL 中，较高的 IL-10 水平与更具侵袭性的疾病相关，这一发现具有重要的潜在临床意义。
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