Endothelin-1 and Interleukin-6 Serum Levels Are Associated with More Severe Vasculopathy in Patients  with Systemic Sclerosis

Ana Maria Gheorghiu¹, Roxana Sfrent-Cornateanu², Daciana Marta³, Raida Oneata⁴, Mihai Bojinca⁴, Stefania Magda⁵, Tudor Constantinescu⁶, Rucsandra Dobrota⁷, Alina Soare⁸, Liviu Macovei¹, Victor Stoica⁴, Constantin Bara² and Carina Mihai⁹, ¹Carol Davila University of Medicine and Pharmacy,Internal Medicine and Rheumatology Department ,,Dr.I.Cantacuzino'' Clinical Hospital, Bucharest, Romania, ²Immunology and Physiopathology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, ³Victor Babes National Institute of Research and Development, Bucharest, Romania, ⁴Carol Davila University of Medicine and Pharmacy, Internal Medicine and Rheumatology Department, Cantacuzino Clinical Hospital, Bucharest, Romania, ⁵Cardiology Department, University Emergency Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, ⁶Marius Nasta National Pneumology Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, ⁷Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich, Zurich, Switzerland, ⁸Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany, ⁹Internal Medicine and Rheumatology Dept., Cantacuzino Clinical Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: capillaroscopy and systemic sclerosis

Session Information

Date: Tuesday, November 7, 2017

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Clinical Aspects and Therapeutics Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

Systemic sclerosis (SSc) is a severe connective tissue disease characterized by vascular and fibrotic changes in the skin and various internal organs. Pathogenesis of SSc includes early-onset vasculopathy with endothelial cell activation, microvascular injury and impaired angiogenesis.

Objectives: We aimed to determine the association of several biological molecules reflecting endothelial cell activation or dysfunction: E- selectin (E-sel), inter-cellular adhesion molecule 1 (ICAM-1), endothelin 1 (ET-1), von Willebrand factor (vWF) and interleukin 6 (IL-6), with distinct capillaroscopic SSc patterns and with more severe disease.

Methods:

Forty consecutive SSc patients attending our EUSTAR SSc clinic, aged [median (IQR)] 52 (18) years, male gender 4/40 (10%), diffuse cutaneous subset (dcSSc) 14/40 (35%) were enrolled in this study. Extensive clinical and nailfold capillaroscopy (NFC) pattern assessment, as well as quantification of serum E-sel, ICAM-1, ET-1, vWF, IL-6 and C-reactive protein (CRP) were performed on all patients. Associations between vascular biomarkers and disease characteristics were evaluated by Mann-Whitney U- test and Spearman correlations. We analyzed the confounding effect of CRP on the association between vascular markers and NFC pattern by multivariable logistic regression.

Results:

NFC “late” pattern was found in 21 patients, while 6 had “early” and 13 had “active” NFC pattern. All 5 vascular biomarkers correlated with each other good to moderately, with r indices varying between 0.660 and 0.332, the only exception being ET-1 which did not correlate with E-sel. Good correlations (r 0.465 to 0.727) were also found between all 5 biomarkers and CRP. Patients with severe vasculopathy, as reflected by the NFC “late” pattern, had higher levels of IL-6 (median 12.06 vs. 3.08 pg/mL, p=0.001), ET-1 (median 2.06 vs 1.59 pg/mL, p=0.029), vWF (median 3284 vs 2730 IU/mL, p=0.013) and E-sel (median 52.6 vs. 42.3 ng/mL, p>0.05), compared to patients with NFC “early” or “active” patterns (Mann-Whitney U- test). In the logistic regression analysis, IL6 (OR (95% CI) 1.175 (1.005, 1.374), p=0.04), ET1 (2.802 (1.157, 6.784), p=0.022) and vWF (1.001 (1.000, 1.003), p=0.034) were significantly associated with “late” capillaroscopy pattern even after adjustment for CRP.

There was a significant, negative correlation between lung transfer for carbon monoxide (DLCO) and E-sel, ICAM-1 (both p<0.001) and vWF (p=0.013). ET-1 was higher in patients with more severe disease (dcSSc, patients positive for anti-topoisomerase antibodies and patients with a history of digital ulcers – all p<0.05).

Conclusion:

Serum biomarkers reflecting endothelial cell activation and/or dysfunction are elevated in patients with more severe SSc-associated vasculopathy even when adjusting for inflammation markers. Together with NFC data they might be used for assessing vasculopathy severity in SSc and identifying patients who would benefit from more aggressive vasoactive treatment.

This work was performed as part of the QUANTICAP project, financed by the UEFISCDI PN-II-PT-PCCA-2013-4-1589 grant.

Disclosure: A. M. Gheorghiu, None; R. Sfrent-Cornateanu, None; D. Marta, None; R. Oneata, None; M. Bojinca, None; S. Magda, None; T. Constantinescu, None; R. Dobrota, None; A. Soare, None; L. Macovei, None; V. Stoica, None; C. Bara, None; C. Mihai, None.

To cite this abstract in AMA style:

Gheorghiu AM, Sfrent-Cornateanu R, Marta D, Oneata R, Bojinca M, Magda S, Constantinescu T, Dobrota R, Soare A, Macovei L, Stoica V, Bara C, Mihai C. Endothelin-1 and Interleukin-6 Serum Levels Are Associated with More Severe Vasculopathy in Patients  with Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/endothelin-1-and-interleukin-6-serum-levels-are-associated-with-more-severe-vasculopathy-in-patients-%e2%80%a8with-systemic-sclerosis/. Accessed .

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