Increased rho kinase activity in temporal artery biopsies from patients with giant cell arteritis

• Published in: Rheumatology (Oxford, England) Vol. 54; no. 3; pp. 554 - 558
• Main Authors: Lally, L., Pernis, A., Narula, N., Huang, W.-T., Spiera, R.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.2015
• Subjects: Aged; Aged, 80 and over; Basic and Translational Science; Biomarkers - metabolism; Biopsy; Case-Control Studies; Cell Differentiation; Cytoskeletal Proteins - metabolism; Female; Giant Cell Arteritis - diagnosis; Giant Cell Arteritis - metabolism; Giant Cell Arteritis - pathology; Humans; Male; Membrane Proteins - metabolism; Microfilament Proteins - metabolism; Predictive Value of Tests; rho-Associated Kinases - metabolism; Sensitivity and Specificity; Temporal Arteries - metabolism; Temporal Arteries - pathology; Th17 Cells - pathology; giant cell arteritis; vasculitis; rho-associated kinases
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/keu364

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.