POS0404 MRI DAVIX INDEX SHOWS BIOLOGICAL FACE VALIDITY: CYTOFLUORIMETRY ANALYSIS TO UNCOVER THE RELATIONSHIP BETWEEN VASCULAR DAMAGE AND ENDOTHELIAL CELL POPULATIONS IN SYSTEMIC SCLEROSIS PATIENTS AND UNDERPIN A CELLULAR PHENOTYPING OF PATIENTS
Authors: S. DI Donato, R. Ross, Y. El-Sherbiny, C. W. Wasson, J. Schmitz, S. Visvanathan, F. Del Galdo
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Circulating endothelial cells (CEC) and their precursors have been shown to correlate to the severity of vascular manifestations in Systemic Sclerosis (SSc)[1], 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. <h3>Objectives:</h3> Here we aimed to assess the frequency of CEC subpopulations in peripheral blood of SSc patients with or without DU disease and to determine their correlation with DAVIX to determine its biological face validity. <h3>Methods:</h3> 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. <h3>Results:</h3> 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), consistent with previous reports. Further, we observed a higher count and number of mature/activated CEC (CD133-/CD146+/CD105+/CD106+) in patient with DU disease (p=0.020 and p=0.039, respectively). Patients with DU disease had a median (IQR) DAVIX of 0.39 (0.27-0.54) vs 0.64 (0.43-1.10) of patients without DU disease (p=0.003), mCEC percentage showed a strong negative correlation with DAVIX (r=-0.529, p&lt;0.001). Accordingly, CEC showed a positive correlation with capillaroscopy pattern (r=0.390, p=0.006), mRSS (r=0.439, p&lt;0.001), and disease duration (r=0.267, p=0.030). and a negative correlation with DLCO (r=-0.281, p=0.030). <h3>Conclusion:</h3> DAVIX showed the strongest correlation of all SSc disease characteristics with the proportion of circulating endothelial cells. Given the known role of these cells in participating in vascular repair following vascular damage, their correlation with DAVIX support the biological face validity of the imaging score. <h3>REFERENCES:</h3> [1] Del Papa N, Colombo G, Fracchiolla N, Moronetti LM, Ingegnoli F, Maglione W, Comina DP, Vitali C, Fantini F, Cortelezzi A. Circulating endothelial cells as a marker of ongoing vascular disease in systemic sclerosis. Arthritis Rheum. 2004 Apr;50(4):1296-304. doi: 10.1002/art.20116. PMID: 15077314. <b>Table 1.</b> Demographics, disease characteristics, and endothelial cell subsets of patients based on the presence of DU disease at baseline. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Stefano Di Donato: None declared, Rebecca Ross: None declared, Yasser El-Sherbiny: None declared, Christopher W Wasson: None declared, Jochen Schmitz Rigel, Eli Lilly, Boehringer-Ingelheim, Sudha Visvanathan Centocor/ J&amp;J, Hoffmann-La Roche, Boehringer Ingelheim, Francesco Del Galdo AstraZeneca, Janssen, AstraZeneca, Abbvie, AstraZeneca, Boehringer-Ingelheim, Capella Biosciences, Chemomab Therapeutics, Ergomed, GSK, Janssen, Mitsubishi-Tanabe.