Rho Kinase Expression in Giant Cell Arteritis: Validating Phosphorylated Ezrin/Radixin/Moesin Intensity Score to Increase Sensitivity of Temporal Artery Biopsy

Abstract

Objective Aberrant Rho-associated protein kinase (ROCK) activity is implicated in several vascular and immunologic disorders. We previously demonstrated increased ROCK activity in histopathologically negative temporal artery biopsies (TABs) in subjects with clinical giant cell arteritis (GCA) compared to those without GCA. This current study aimed to examine ROCK activity in a larger cohort of biopsy-negative GCA subjects and to validate the prior findings. Methods. Based on clinical data 6 months after TAB, subjects were categorized into 2 groups: biopsy-negative GCA and controls without GCA. Paraffin-embedded TABs were stained for phosphorylated ezrin/radixin/ moesin (pERM), a surrogate of ROCK activity, and scored by 2 pathologists blinded to clinical diagnosis using a previously derived scoring system measuring staining intensity in 3 areas of the vessel. Results. Thirty-six subjects with biopsy-negative GCA and 43 controls were analyzed. The mean (SD) pERM intensity score in non-GCA subjects was 3.9 (1.4), compared to 5.0 (1.4) in those with GCA (P = 0.002). Using the predetermined cut-off of 4 to define high pERM intensity, subjects with GCA were significantly more likely to have a high pERM intensity score compared to non-GCA (odds ratio 3.67, 95% CI 1.19-11.36; P = 0.02. The sensitivity of high pERM intensity score for diagnosis of GCA in histologically negative TABs was 86% (95% CI 70-95). Conclusion. In this well-characterized cohort, those with biopsy-negative GCA had significantly higher pERM intensity scores compared to subjects without GCA. pERM staining has diagnostic significance in enhancing the sensitivity of TAB and may help to define the clinically important group of biopsy-negative GCA.