López De Padilla Consuelo M, Hein Molly S, Crowson Cynthia S, Choo Christopher S, Green Abigail B, Petri Michelle, Bilgic Hatice, Baechler Emily C, Reed Ann M
Division of Rheumatology, Mayo Clinic, Rochester, MN, USA.
Division of Rheumatology, Mayo Clinic, Rochester, MN, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
SAGE Open Med. 2013 Nov 29;1:2050312113514404. doi: 10.1177/2050312113514404. eCollection 2013.
We investigated ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif, member 13) messenger RNA levels as a biomarker of disease features in systemic lupus erythematosus.
We measured and compared messenger RNA (mRNA) levels of ADAMTS13 in peripheral blood cells in patients with systemic lupus erythematosus and healthy control subjects by whole-genome microarray. We retrospectively analyzed the correlations of ADAMTS13 mRNA expression with clinical features, laboratory parameters, therapeutic features, and disease activity (according to the Systemic Lupus Erythematosus Disease Activity Index). We also examined the association of three single nucleotide polymorphisms (rs4962145, rs2285467, and rs685523) of the ADAMTS13 gene with patient characteristics.
In 309 patients, the median ADAMTS13 mRNA expression levels were significantly higher in blood cells of systemic lupus erythematosus patients than in 23 healthy controls (p = .03). Notably, ADAMTS13 mRNA expression levels were significantly higher in systemic lupus erythematosus patients with a history of stroke (p = .02) or transient ischemic attack (p = .02). Among the three single nucleotide polymorphisms analyzed, rs2285467 was significantly associated with stroke (p = .03) and anticardiolipin antibodies (p = .04).
Increased expression of ADAMTS13 mRNA in blood cells is associated with the presence of ischemic cerebrovascular disease in systemic lupus erythematosus patients and suggests a potential role for ADAMTS13 in the pathogenesis of ischemic cerebrovascular disease in these patients.
我们研究了ADAMTS13(含Ⅰ型血小板反应蛋白基序的解聚素样金属蛋白酶13)信使核糖核酸水平,将其作为系统性红斑狼疮疾病特征的生物标志物。
我们通过全基因组微阵列测量并比较了系统性红斑狼疮患者和健康对照者外周血细胞中ADAMTS13的信使核糖核酸(mRNA)水平。我们回顾性分析了ADAMTS13 mRNA表达与临床特征、实验室参数、治疗特征及疾病活动度(根据系统性红斑狼疮疾病活动指数)之间的相关性。我们还检测了ADAMTS13基因的三个单核苷酸多态性(rs4962145、rs2285467和rs685523)与患者特征的关联。
在309例患者中,系统性红斑狼疮患者血细胞中的ADAMTS13 mRNA表达水平中位数显著高于23例健康对照者(p = 0.03)。值得注意的是,有中风病史(p = 0.02)或短暂性脑缺血发作病史(p = 0.02)的系统性红斑狼疮患者中,ADAMTS13 mRNA表达水平显著更高。在分析的三个单核苷酸多态性中,rs2285467与中风(p = 0.03)和抗心磷脂抗体(p = 0.04)显著相关。
血细胞中ADAMTS13 mRNA表达增加与系统性红斑狼疮患者缺血性脑血管疾病的存在相关,提示ADAMTS13在这些患者缺血性脑血管疾病发病机制中可能发挥作用。