| Popis: |
Background: 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. This study aimed to examine ROCK activity in a larger cohort of biopsy-negative GCA subjects and to validate the prior findings. Methods: Subjects were categorized into 2 groups based on clinical data 6-months after TAB: biopsy-negative GCA and controls without GCA. Paraffin-embedded TAB were stained for phosphorylated ezrin/radixin/moesin (pERM), a surrogate of ROCK activity, and scored by two pathologists blinded to clinical diagnosis using a previously derived scoring system. 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 correlating with ROCK activity. TAB sections were also stained for unphosphorylated ERM, the inactive protein. Results: Thirty six subjects with biopsy-negative GCA and 43 controls were analyzed. There were no differences between groups in age, sex and corticosteroid dose. The mean 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, OR 3.67, 95%CI :1.19,11.36; p= 0.019. The sensitivity of high pERM intensity score for diagnosis of GCA in histologically negative TAB was 86%, 95%CI: 70,95. Conclusions:. In this well characterized cohort, those with GCA and negative biopsies had significantly higher pERM intensity scores in TAB specimens compared to subjects without GCA. 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 |
