Background/Purpose: Aberrant rho-kinase (ROCK) activity is implicated in pathogenesis of several vascular and immunologic disorders. We previously demonstrated evidence of increased ROCK activity in histopathologically negative temporal artery biopsies (TAB) of subjects with clinical giant cell arteritis (GCA) compared to those without GCA. The aim of this study was to validate a ROCK activity score in a large cohort of GCA patients.

Methods: TAB obtained as part of an international study examining the role of ultrasound in GCA were utilized. Only histologically negative TABs were used for this study. Subjects were categorized into 2 groups, those who were diagnosed with GCA despite negative TAB at 6 months after biopsy and those with negative TAB ultimately felt not to have GCA. Paraffin-embedded TAB were stained for phosphorylated ezrin/radixin/moesin (pERM), a surrogate of ROCK activity, and reviewed by a pathologist blinded to clinical diagnosis. Three areas of the vessel (intima, adventitial and vasa vasorum) were scored for staining intensity on a scale of 0–2, with a maximum possible score of 6 for each TAB. As determined a priori, scores ³4 were considered a high pERM intensity score suggesting ROCK activity. TAB sections were also stained for unphosphorylated ERM, the inactive protein.

Results: Biopsies of 36 subjects with TAB-negative GCA were identified and compared to biopsies of 43 subjects without GCA. There were no differences between the 2 groups in age, sex and corticosteroid dose. The mean pERM intensity score in non-GCA subjects was 3.9 ± 1.4 compared to mean pERM intensity score of 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 nearly4 times more likely to have a high pERM intensity score compared to non-GCA, OR 3.67, 95%CI :1.19,11.36; p= 0.019. The sensitivity of high pERM intensity score for the diagnosis of GCA in histologically negative TAB was 86%, 95%CI: 70,95. In GCA subjects, the ERM staining was less intense in all areas of the TAB specimens compared to the pERM staining, suggesting activation of the ROCK pathway.

Conclusion: In this large cohort of well characterized subjects, those with GCA and negative biopsies had significantly higher pERM intensity scores in TAB specimens compared to subjects without GCA. These results are concordant with previously published pilot data. pERM staining has diagnostic significance in enhancing the sensitivity of TAB, and helps to define the clinically important group of biopsy-negative GCA. The ROCK pathway warrants further investigation in GCA and may be a potential therapeutic target.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rho-kinase-ezpression-in-giant-cell-arteritis-validating-perm-intensity-score-as-a-method-of-increasing-sensitivity-of-temporal-artery-biopsy/