Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University Hospital, Sölvegatan 23, Lund, Sweden.
Blood. 2010 Sep 16;116(11):1951-7. doi: 10.1182/blood-2010-03-274605. Epub 2010 Jun 10.
Patients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease, and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in patients with SLE and healthy controls, and the gene and protein expression of a subset of differentially expressed genes was further investigated and correlated to platelet activation status. Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (P < .0001) were found to be up-regulated in platelets from SLE patients compared with healthy volunteers. Notably, patients with a history of vascular disease had increased expression of type I IFN-regulated proteins as well as more activated platelets compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFNα that up-regulates the megakaryocytic type I IFN-regulated genes and proteins. This could affect platelet activation and contribute to development of vascular disease in SLE. In addition, platelets with type I IFN signature could be a novel marker for vascular disease in SLE.
系统性红斑狼疮（SLE）患者发生心血管疾病的风险显著增加，而传统心血管危险因素无法解释这种风险增加。我们使用微阵列技术检测 SLE 患者和健康对照者的血小板转录组，进一步研究了一组差异表达基因的基因和蛋白表达，并将其与血小板活化状态相关联。实时 PCR 用于确认 SLE 患者的 I 型干扰素（IFN）基因特征，发现与健康志愿者相比，SLE 患者的血小板中 PRKRA、IFITM1 和 CD69（P <.0001）等 IFN 调节蛋白表达上调。值得注意的是，与无血管疾病的患者相比，有血管疾病病史的患者 I 型 IFN 调节蛋白的表达增加，血小板也更活跃。我们认为，干扰素免疫复合物刺激产生 IFNα，上调巨核细胞 I 型 IFN 调节基因和蛋白。这可能会影响血小板的活化，导致 SLE 患者发生血管疾病。此外，具有 I 型 IFN 特征的血小板可能是 SLE 血管疾病的一个新标志物。
