Background/Purpose: Circulating endothelial cells (CEC) and their precursors have been shown to correlate to the severity of vascular manifestations in Systemic sclerosis¹, such as Digital Ulcers (DUs) and Pulmonary Artery Hypertension (PAH). Recently, the MRI based Digital Artery Volume Index (DAVIX) has been shown to predict activity of DUs Disease and to be correlated with Diffusion Lung Capacity of Co (DLCO) which is known to be reduced prior to the diagnosis of PAH.

Methods: Consecutive adult patients fulfilling the 2013 ACR/EULAR criteria enrolled in a national observational cohort study (Stratification for Risk of Progression in SSc – STRIKE SSc) were invited to take an MRI angiography of the dominant hand for DAVIX calculation, as previously described, and to donate a sample of 9 mL of blood for cell cytofluorimetry, following appropriate informed consent. Subfamilies of circulating endothelial cells (CECs) were measured by flow-cytometry gating for CD45, CD3, CXCR4, and then, on CD45- cells, further gating for CD43, CD31, CD133, CD146, CD106, and CD105. CEC subpopulations were reported as absolute numbers and as percentages of the overall endothelial cells (EC). Clinical and demographic characteristics included: Leroy subset, age, gender, disease duration, antibody specificity, history of DUs, presence of telangiectasia, FVC%, DLCO% FVC/DLCO ratio, and current medications. Categorical data were reported as counts (%) and continuous data as means (SD) or medians (IQR), as appropriate. Comparisons were performed with Student’s t, Wilcoxon’s test, Fisher’s, or Chi tests, as appropriate. Correlations were performed using Spearman’s or Pearson’s r.

Results: Sixty-eight patients were recruited in this sub study of STRIKE with an overall median (IQR) age of 57 (49-66). Demographic and clinical differences across patients with and without DUs disease are reported in Table 1. Patients with DUs disease presented a higher count and proportion of CD133-CD146+ CEC (p=0.037 and p=0.028, respectively) and, conversely had significantly lower percentage of CD133-/CD146- cells (p=0.03).

Of the CEC subfamilies, CD133-/CD146+/CD105+/CD106+ mCEC were significantly higher in patients with DUs disease both in absolute count and proportion (p=0.020 and p=0.039, respectively). Furthermore, in the whole cohort, mCEC percentage showed a strong negative correlation with DAVIX (r=-0.529, p< 0.001). Consistently, mCEC percentage had a positive correlation with capillaroscopy pattern (r=0.390, p=0.006), mRSS (r=0.439, p< 0.001), and disease duration (r=0.267, p=0.030). mCEC absolute count showed a significant correlation with FVC% (r=-0.293, p=0.022) and DLCO (r=-0.281, p=0.030).

Conclusion: DAVIX showed the strongest correlation of all SSc disease characteristics with mCEC percentage. These cells participate in vascular repair and are mobilized in case of vascular damage, therefore showing DAVIX’s biologic face validity. A potential classification system, using DAVIX and clinical manifestations, may stratify “vascular” SSc categories and is substantiated by differential levels of endothelial cell subpopulations reflective of vascular remodelling processes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mri-davix-index-is-an-imaging-biomarker-for-endothelial-damage-of-systemic-sclerosis-digital-ulcers/