Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Recent findings have implicated CXCL4 in the pathogenesis of systemic sclerosis (SSc), while also indicating a potential role of this chemokine as a biomarker in SSc. Herein, we examined whether plasma levels of CXCL4-L1, a non-allelic variant of CXCL4, which displays a constitutive pathway of secretion by platelets and smooth muscle cells and is a stronger inhibitor of angiogenesis compared to CXCL4, differ between SSc patients and healthy controls. Furthermore, we investigated if CXCL4-L1 levels correlate with clinical and capillaroscopy features of SSc patients.
Methods: CXCL4 plasma levels were measured by ELISA in 94 SSc patients, 5 patients with very early diagnosis of SSc (VEDOSS) and 74 healthy controls. CXCL4-L1 plasma levels were measured by ELISA in 68 of 94 SSc patients, 9 VEDOSS patients and 58 of 74 healthy controls. Nailfold Video Capillaroscopy (NVC) and clinical data were collected from all patients. To compare levels of expression of CXCL4-L1 mRNA in peripheral blood mononuclear cells (PBMCs) between SSc patients with and without pulmonary arterial hypertension (PAH) and healthy controls we used information from the publicly available online microaray dataset GSE33463. Comparisons were performed using the Mann-Whitney U-test.
Results: Plasma levels of CXCL4 were significantly higher in SSc patients (mean±SD= 62.84 ± 82.32ng/ml) compared to controls (mean±SD= 32.67 ± 33.48ng/ml, p=0.0004) and correlated significantly with smocking (B=51.74, p=0.024) and presence of interstitial lung disease on high resolution computed tomography of the chest (B=33.47, p=0.042), after adjustment for age and gender. CXCL4-L1 plasma levels were increased in SSc patients (mean±SD=205.54±199.39pg/ml), compared to both VEDOSS patients (mean±SD=75.67±51.00 pg/ml, p=0.0158) and controls (mean±SD=82.29±114.88pg/ml, p< 0.0001) and correlated significantly with capillaroscopic parameters [dilatation score, (B=116.3, p=0.007), micohemorrhages score, (Β=185.87, p=0.012)]. After correction for age and gender correlation with microhemorrhages score remained marginally significant (B=146.26, p=0.063). In terms of mRNA expression CXCL4-L1 was increased in PBMCs of SSc patients compared to controls, as well as in PBMCs of SSc patients with PAH compared to SSc patients without PAH.
Conclusion: CXCL4-L1, an angiogenesis inhibitor, is increased in the peripheral blood of SSc patients both at the mRNA and protein levels. Correlation of CXCL4-L1 levels with capillaroscopic indices and PAH in these patients suggest that further prospective studies should examine whether CXCL4-L1 may serve as biomarker for vascular damage in SSc.
To cite this abstract in AMA style:Bournia V, Patsouras M, Vlachoyiannis N, Tzioufas A, Sfikakis P, Vlachoyiannopoulos P. CXCL4-L1 Levels Are Elevated in Systemic Sclerosis Patients and Correlate with Pulmonary Arterial Hypertension and Capillaroscopic Indices of Vascular Damage [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/cxcl4-l1-levels-are-elevated-in-systemic-sclerosis-patients-and-correlate-with-pulmonary-arterial-hypertension-and-capillaroscopic-indices-of-vascular-damage/. Accessed January 18, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cxcl4-l1-levels-are-elevated-in-systemic-sclerosis-patients-and-correlate-with-pulmonary-arterial-hypertension-and-capillaroscopic-indices-of-vascular-damage/