嘌呤核苷磷酸化酶与系统性红斑狼疮发病的相关性研究

Purine nucleoside phosphorylase is associated with the pathogenesis of systemic lupus erythematosus

嘌呤核苷磷酸化酶(PNP)介导嘌呤降解,异常时会影响DNA合成。本研究探讨PNP与SLE发病的相关性。检测了诊断明确的42例系统性红斑狼疮患者和48例正常对照者PBMC、12例狼疮肾炎患者肾穿样本和10例肾癌患者癌旁正常肾脏样本中PNP的表达格局,继而分析了PNP与SLE患者的临床表现。由于I型干扰素通路的异常活化在SLE发病中起重要作用,因此本研究还分析了PNP表达与干扰素积分的相关性。结果表明:与正常人相比,狼疮病人PBMC和肾脏组织中PNP表达水平均显著性降低。进一步通过干扰素积分相关性分析发现,狼疮肾炎患者肾脏组织PNP的表达水平与干扰素积分呈负相关,提示PNP可能参与I型干扰素通路的调节。本研究表明狼疮患者PNP表达异常,可能参与SLE的发病。

Abnormal degradation of purine mediated by urine nucleoside phosphorylase （PNP） affects the synthesis of DNA. In this study, we investigated the correlation between PNP expression and the activity of systemic lupus erythematosus（SLE）. We measured the mRNA levels of PNP in PBMC from 42 patients with SLE and 48 healthy controls, as well as kidney biopsies from 12 patients with SLE lupus nephritis and 10 control patients with kidney cancer. The association of PNP expression with the manifestations of lupus was then analyzed. Since type I IFN signaling is crucial for the development of lupus, we also ana- lyzed the correlation between PNP expression and IFN scores. We found that the levels of PNP in both PBMC and kidney tis- sues from lupus patients were significantly reduced compared with disease controls. In particular, PNP expression is negatively correlated with IFN scores, suggesting that PNP might be involved in regulating type I IFN signaling. Taken together, our da- ta demonstrated that the expression of PNP is dysregulated in lupus patients. These findings indicate that PNP might play a role in the pathogenesis of SLE.