Department of Rheumatology, Hospital for Special Surgery, Department of Medicine, Weill-Cornell Medical College, Autoimmunity and Inflammation Program, Hospital for Special Surgery and Department of Clinical Pathology and Laboratory Medicine, Weill-Cornell Medical College, New York, NY, USA. Department of Rheumatology, Hospital for Special Surgery, Department of Medicine, Weill-Cornell Medical College, Autoimmunity and Inflammation Program, Hospital for Special Surgery and Department of Clinical Pathology and Laboratory Medicine, Weill-Cornell Medical College, New York, NY, USA.
Department of Rheumatology, Hospital for Special Surgery, Department of Medicine, Weill-Cornell Medical College, Autoimmunity and Inflammation Program, Hospital for Special Surgery and Department of Clinical Pathology and Laboratory Medicine, Weill-Cornell Medical College, New York, NY, USA.
Rheumatology (Oxford). 2015 Mar;54(3):554-8. doi: 10.1093/rheumatology/keu364. Epub 2014 Sep 10.
Aberrant rho kinase (ROCK) activity is implicated in the pathogenesis of several vascular diseases and is associated with Th17 differentiation. Th17 immune response is recognized in the pathogenesis of GCA. The aim of this study was to assess ROCK activity in GCA.
All patients who underwent temporal artery biopsy (TAB) at a tertiary care centre over 5 years were identified and charts reviewed. Subjects were categorized into three groups: TAB-positive GCA, TAB-negative GCA and age- and sex-matched controls. TABs were stained for phosphorylated ezrin/radixin/moesin (pERM), a surrogate of ROCK activity, and reviewed by a pathologist blinded to clinical status. Three areas were scored for staining intensity on a scale of 0-2, with a maximum possible score of 6.
Nineteen subjects with TAB-positive GCA, 17 with TAB-negative GCA and 18 controls were analysed. Compared with controls, GCA subjects with either positive or negative TABs had significantly higher pERM intensity scores (P = 0.0109). Adjusting for diabetes, hypertension, prednisone and statin use, GCA subjects still had higher pERM scores [odds ratio 7.3 (95% CI 1.9, 25.9), P = 0.0046]. The high pERM score had a sensitivity of 90% and a negative predictive value of 91% for the diagnosis of GCA in those with a negative TAB, compared with 51% sensitivity for histopathology alone.
Subjects with GCA had more intense pERM staining in TAB specimens compared with age- and sex-matched controls, regardless of whether TAB was positive or negative by routine histopathology, suggesting increased ROCK activity in GCA. The ROCK pathway warrants further investigation in GCA, as it may have diagnostic significance in enhancing the sensitivity of TAB.
异常的 Rho 激酶（ROCK）活性与几种血管疾病的发病机制有关，并与 Th17 分化有关。Th17 免疫反应在 GCA 的发病机制中被识别。本研究旨在评估 GCA 中的 ROCK 活性。
在一家三级保健中心，对过去 5 年内进行颞动脉活检（TAB）的所有患者进行了识别，并对其病历进行了回顾。受试者分为三组：TAB 阳性的 GCA、TAB 阴性的 GCA 和年龄与性别匹配的对照组。对 TAB 进行磷酸化 ezrin/radixin/moesin（pERM）染色，pERM 是 ROCK 活性的替代物，由对临床状况不知情的病理学家进行评估。对染色强度进行 0-2 分的评分，最高评分为 6 分。
对 19 例 TAB 阳性的 GCA、17 例 TAB 阴性的 GCA 和 18 例对照组进行了分析。与对照组相比，TAB 阳性或阴性的 GCA 患者的 pERM 强度评分显著更高（P = 0.0109）。调整糖尿病、高血压、泼尼松和他汀类药物的使用后，GCA 患者的 pERM 评分仍更高[比值比 7.3（95%CI 1.9，25.9），P = 0.0046]。对于 TAB 阴性的患者，高 pERM 评分对 GCA 的诊断具有 90%的敏感性和 91%的阴性预测值，而单独进行组织病理学检查的敏感性为 51%。
与年龄和性别匹配的对照组相比，无论 TAB 通过常规组织病理学检查是阳性还是阴性，GCA 患者的 TAB 标本中的 pERM 染色更强烈，提示 GCA 中 ROCK 活性增加。ROCK 通路在 GCA 中值得进一步研究，因为它可能在提高 TAB 的敏感性方面具有诊断意义。
