Gualtierotti Roberta, Ingegnoli Francesca, Griffini Samantha, Grovetti Elena, Borghi Maria Orietta, Bucciarelli Paolo, Meroni Pier Luigi, Cugno Massimo
Lupus Clinic, Divisione e Cattedra di Reumatologia, Università degli Studi di Milano, Istituto G. Pini, Milan, Italy.
Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Cattedra di Reumatologia, Istituto G. Pini, Milan, Italy.
Microvasc Res. 2017 Sep;113:22-28. doi: 10.1016/j.mvr.2017.04.004. Epub 2017 Apr 25.
Raynaud's phenomenon (RP) can be the first manifestation of systemic sclerosis (SSc) or other connective tissue diseases (CTDs), often preceding an overt disease by years. It is not known if markers of endothelial damage are detectable in those RP patients who subsequently develop a CTD.
We studied 82 RP patients at their first evaluation to correlate the levels of endothelial markers with the subsequent development of an overt disease 36months later. We measured plasma levels of tissue-type plasminogen activator (t-PA) and von Willebrand factor (vWF), two markers of endothelial damage, and interleukin-6 (IL-6), a pro-inflammatory cytokine. Thirty sex- and age-matched healthy subjects (HS) served as controls.
At baseline, 67 patients showed capillaroscopic normal pattern (CNP) and 15 patients, of which 11 were very early SSc, had capillaroscopic scleroderma pattern (CSP). Plasma levels of t-PA, vWF and IL-6 were higher in patients with CNP (p=0.0001) than in HS and even much higher in patients with CSP (p=0.0001). In patients with CNP and RP of recent onset (<18months), vWF plasma levels were higher when autoantibodies were present (p=0.020). After 36months, among 48 RP patients with CNP who remained in follow-up, 24 were diagnosed as primary and 24 as secondary RP. In secondary RP, basal levels of t-PA, IL-6 and particularly vWF were higher than in primary RP (p=0.005, p=0.004, p=0.0001 respectively) and HS (p=0.0001 for all).
Our findings indicate that markers of endothelial damage are elevated in RP patients who subsequently develop SSc or other CTDs, even in the absence of capillaroscopic abnormalities.
雷诺现象（RP）可能是系统性硬化症（SSc）或其他结缔组织病（CTD）的首发表现，通常在显性疾病出现前数年就已存在。目前尚不清楚在那些随后发展为CTD的RP患者中是否能检测到内皮损伤标志物。
我们在82例RP患者首次评估时进行研究，以将内皮标志物水平与36个月后显性疾病的后续发展情况相关联。我们测量了血浆组织型纤溶酶原激活物（t-PA）和血管性血友病因子（vWF）这两种内皮损伤标志物以及促炎细胞因子白细胞介素-6（IL-6）的水平。30名年龄和性别匹配的健康受试者（HS）作为对照。
基线时，67例患者显示毛细血管镜检查正常模式（CNP），15例患者（其中11例为极早期SSc）有毛细血管镜检查硬皮病模式（CSP）。CNP患者的t-PA、vWF和IL-6血浆水平高于HS（p = 0.0001），而CSP患者的这些水平更高（p = 0.0001）。在近期发病（<18个月）的CNP和RP患者中，存在自身抗体时vWF血浆水平更高（p = 0.020）。36个月后，在48例仍在随访的CNP RP患者中，24例被诊断为原发性RP，24例为继发性RP。在继发性RP中，t-PA、IL-6尤其是vWF的基础水平高于原发性RP（分别为p = 0.005、p = 0.004、p = 0.0001）和HS（均为p = 0.0001）。
我们的研究结果表明，即使在没有毛细血管镜异常的情况下，随后发展为SSc或其他CTD的RP患者的内皮损伤标志物也会升高。
