title: Increased rho kinase activity in temporal artery biopsies from patients with giant cell arteritis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. lallyl@hss.edu.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Lally
authors.affiliation: 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.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pernis
authors.affiliation: 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.
authors.forename: Navneet
authors.initials: N
authors.lastname: Narula
authors.affiliation: 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.
authors.forename: Wei-Ti
authors.initials: WT
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Robert
authors.initials: R
authors.lastname: Spiera
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D013700:Giant Cell Arteritis / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013699:Temporal Arteries / Q000378:metabolism* / Q000473:pathology*; D058504:Th17 Cells / Q000473:pathology; D054460:rho-Associated Kinases / Q000378:metabolism*; D000099149:Ezrin
chemical_list: D015415:Biomarkers; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D054460:rho-Associated Kinases; D000099149:Ezrin; C071058:moesin; C071776:radixin
keywords: giant cell arteritis; rho-associated kinases; vasculitis