POS0134 LEARNING FROM LONGITUDINAL DATA IN CHILDHOOD ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: WHICH BIOMARKERS HAVE PREDICTIVE VALUE FOR ENDOTHELIAL INVOLVEMENT?

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; pp. 286 - 287
• Main Authors: Bergkamp, S, Bergkamp, N, Wahadat, M J, Gruppen, M, A Nassar-Sheikh Rashid, Kuijpers, T, Tas, S, Smit, M, Kamphuis, S, J M Van den Berg, D Schonenberg-Meinema
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2023
• Subjects: Angiogenesis; Angiopoietin; Arteriosclerosis; Arthritis; Atherosclerosis; Biomarkers; Cardiovascular diseases; Children; CXCL10 protein; CXCL12 protein; E-selectin; Endothelial cells; Endothelium; Intercellular adhesion molecule 1; IP-10 protein; Lupus; Monocyte chemoattractant protein 1; P-selectin; Patients; Pentraxins; Risk factors; SDF-1 protein; Serum levels; Systemic lupus erythematosus; Thrombomodulin; Vascular cell adhesion molecule 1; Vascular endothelial growth factor
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.4141

BackgroundIn (childhood-onset) systemic lupus erythematosus ((c)SLE), patients have an increased risk of developing premature atherosclerosis [1]. The pathophysiological mechanisms for this atherosclerosis are not completely understood. Besides traditional risk factors, the endothelium plays a major role [2]. Dysregulated endothelial cell markers and proteins involved in endothelial function in SLE are not always correlated to disease activity, which could mean that the endothelium stays in a dysregulated state in SLE, even with low disease activity (Bergkamp et al., submitted). However, previous studies were mostly cross-sectional and only performed in adult SLE, while childhood-onset SLE (cSLE) has a longer and more severe course [3,4].ObjectivesTo measure the serum levels of a panel of SLE-associated markers involved in endothelial cell (EC) function, in longitudinal samples of cSLE patients (active vs. low SLE disease activity index (SLEDAI)) and to compare them with healthy controls and assess their correlation with disease activity.MethodsBlood samples and patient characteristics were collected from a multicentre longitudinal cSLE study and compared with age- and sex-matched healthy controls (HC). Disease activity was evaluated by SLEDAI-2K, with cut-offs for active (>4) versus low (≤4) activity. Serum levels of CXCL12 (SDF-1), TWEAK, VEGF, CXCL10 (IP-10), ADAMTS13, Angiopoietin-2, Pentraxin-3, E-Selectin, Thrombomodulin, P-selectin, CCL2 (MCP-1), VCAM-1, ICAM-1, vWF-A2 and Gas6 were measured in two cSLE samples (t=1 and t=2) and in HC (1 sample). Patient groups and healthy controls were compared by t-tests and ANOVA, with significance for p < 0.05. Correlations between marker serum levels and SLEDAI were calculated with Pearson correlation.ResultsThis study included 47 cSLE patients (30 treatment-naïve) and 42 healthy controls. Mean age at diagnosis in cSLE was 14 (± 2.33) years. Median SLEDAI at t=1 was 12 (IQR 6-18). Median SLEDAI t=2 was 2.5 (IQR 2-6). Time between two blood samples was 14.5 months (IQR 9-24 months). Median disease duration at t=1 was 0 months (IQR 0-18 months) and at t=2 16.5 months (IQR 10-53 months). Ethnic background in patients was 42.6% Caucasian, 36.2% African/Afro-Caribbean, 8.5% North-African/Middle East, 4.3% Asian and 8.5% mixed/other ethnic background. At t=1, serum levels of CXCL10 (p=0.01), Thrombomodulin (p=0.03) and VCAM-1 (p=0.01) were higher in the group with active cSLE compared to those with low disease activity. Serum levels for CXCL10, Pentraxin-3, Thrombomodulin, P-selectin, vWF-A2 and Gas6 correlated with SLEDAI score. Angiopoietin-2 and VCAM-1 were upregulated in cSLE patients versus healthy controls (both p<0.001),but not related to disease activity (figure 1A). Levels of CXCL10, Angiopoietin-2, Pentraxin-3, E-Selectin, CCL2, VCAM-1 and vWF-A2 decreased over time, while serum levels of TWEAK increased over time (all p<0.05) (figure 1B).ConclusionAt different time points, serum levels of Angiopoietin-2 (t=1), VCAM-1 (t=1) and TWEAK (t=2) were increased in cSLE patients, irrespective of disease activity. These markers represent activation of ECs with vascular inflammation, EC activation and a pro-angiogenic state. The endothelium in cSLE seems to stay in an active state, even in low disease activity (SLEDAI≤4). Our findings suggest that some EC markers might be useful as biomarkers for predicting the ongoing risk for endothelial dysfunction in cSLE.References[1]Ardoin SP, Schanberg LE, et al. Laboratory markers of cardiovascular risk in pSLE: the APPLE baseline cohort. Lupus. 2010 PMID: 20861207[2]Westerweel PE, Luyten RK, et al. Premature atherosclerotic cardiovascular disease in SLE. Arthritis Rheum. 2007 May; 1384-96. PMID: 17469095[3]Brunner HI, Silverman ED et al. Difference in disease features between cSLE and aSLE. Arthr and rheum. 2008;58(2):556-62[4]Groot N, Shaikhani D, R, et al. Long-Term Clinical Outcomes in a Cohort of Adults With cSLE. Arthritis Rheumatol. 2019;71(2):290-301Acknowledgements:NIL.Disclosure of InterestsNone Declared.