Autoantibody Subtype does not Impact Peripheral Endothelial Function and Hemodynamics in Systemic Sclerosis

Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular dysfunction that leads to vasculopathy and fibrosis. Autoantibody assessment is included as part of the diagnostic criteria and has implications for organ‐involvement and disease. The purpose of this study was to assess peripheral endothelial function and hemodynamics across a range of autoantibody subtypes among patients with SSc. We hypothesized that endothelial function would differ between autoantibody subtypes, with greater dysfunction in the more severe autoantibody subtype (i.e., topoisomerase; SCL70). To our knowledge, this is the first study with an adequate sample size with endothelial function measurements in several autoantibody subtypes. Patients that met ACR/EULAR SSc classification criteria were enrolled at a single center. Endothelial function was assessed in study subjects with the flow‐mediated dilation (FMD) technique using a 5‐min suprasystolic occlusion period and following published guidelines. A blood pressure cuff was placed on the right arm, distal to the ultrasound Doppler probe on the brachial artery. Simultaneous measurements of brachial artery vessel diameter and blood velocity were performed using a linear array transducer operating in duplex mode. The brachial artery was insonated approximately midway between the antecubital and axillary regions, and measurements of diameter and blood velocity were obtained continuously at rest and for 2 minutes after cuff deflation. To determine autoantibody status, patient blood samples were collected, and an antigen‐specific enzyme‐linked immunosorbent assay (ELISA) was performed. One‐way ANOVA was used to determine the variance between groups. Patients with SSc (n=139) were matched for age and disease duration, then grouped by autoantibody status (centromere, topoisomerase, RNA polymerase III, other SSc‐associated autoantibodies, and anti‐nuclear antibody positive, but with no known autoantibody present). In this cohort of patients with SSc, basic clinical characteristics did not differ between autoantibody groups (p>0.05). Baseline brachial artery diameter and blood flow were similar across autoantibody groups (p=0.43 and p=0.82, respectively). Post‐ischemic peak reactive hyperemia and total hyperemia were not different between autoantibody groups (p=0.84 and p=0.99, respectively). There was no difference in absolute % FMD (p=0.11), and this similarity persisted with normalization to the shear rate at peak dilation (p=0.34). We observed no difference in peripheral endothelial function or hemodynamics (i.e., hyperemia and shear) based on autoantibody status. Thus, these data suggest that autoantibody status does not differentially affect peripheral endothelial function and hemodynamics in patients with SSc.Support or Funding InformationFunding Information: Funded in part by NIH R01 AG048366, R01 AG050238, R01 AG060395, K99 AT010017, US Department of Veteran Affairs I01 CX001183