Diagnosis
Prediction of organ involvement in systemic sclerosis by serum biomarkers and peripheral endothelial function
S.-Y. Kawashiri1, A. Nishino2, T. Igawa3, A. Takatani4, T. Shimizu5, M. Umeda6, S. Fukui7, A. Okada8, T. Suzuki9, T. Koga10, N. Iwamoto11, K. Ichinose12, M. Tamai13, M. Nakashima14, A. Mizokami15, N. Matsuoka16, K. Migita17, F. Ogawa18, S. Ikeda19, K. Maemura20, H. Nakamura21, T. Origuchi22, T. Maeda23, A. Kawakami24
- Departments of Community Medicine and Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. shin-ya@nagasaki-u.ac.jp
- Department of Immunology and Rheumatology, and Center for Comprehensive Community Care Education, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Internal Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.
- Department of Internal Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Centre for Rheumatic Diseases, Kurume University Medical Centre, Kurume, Japan.
- Department of Rheumatology, Isahaya General Hospital, Isahaya, Japan.
- Nagasaki Medical Hospital of Rheumatology, Nagasaki, Japan.
- Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
- Ogawa Dermatology and Allergy Clinic, Nagasaki, Japan.
- Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
- Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
CER10806
2018 Vol.36, N°4 ,Suppl.113
PI 0102, PF 0108
Diagnosis
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PMID: 29652651 [PubMed]
Received: 12/09/2017
Accepted : 05/03/2018
In Press: 12/04/2018
Published: 29/09/2018
Abstract
OBJECTIVES:
To identify prognostic factors among serum biomarkers and endothelial vasodilator function findings in patients with systemic sclerosis (SSc).
METHODS:
This is a clinical observational study. We assessed 60 consecutive SSc patients (44 limited cutaneous-type, 16 diffuse cutaneous-type). Circulating growth differentiation factor-15 (GDF-15), placenta growth factor (PlGF), endostatin, vascular endothelial growth factor (VEGF), and pentraxin 3 (PTX3) were measured by ELISA. Peripheral endothelial function was measured by forearm blood dilatation response to brachial artery occlusion using noninvasive plethysmography (EndoPAT2000), which is associated with nitric-oxide-dependent vasodilatation and yields a reactive hyperemia index (RHI). We evaluated whether abnormalities in these values were associated with type of SSc - namely, diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc) - or organ involvement including interstitial lung disease (ILD), digital ulcer (DU) and estimated right ventricular systolic pressure (RVSP) by echocardiography >30 mmHg.
RESULTS:
SSc patients showed significantly elevated serum GDF-15, PlGF, endostatin and VEGF but not PTX3 compared with controls. GDF-15 and PlGF were high in dcSSc patients. EndoPAT-RHI was low, and incidence of RVSP >30 mmHg was high in dcSSc. Multivariate analysis revealed that elevated GDF-15 was highly predictive of dcSSc, ILD or RVSP >30 mmHg. PlGF for DU was also found. Conversely, a low EndoPAT-RHI value was predictive of the presence of dcSSc, ILD or DU.
CONCLUSIONS:
This is the first study to inclusively investigate the relationships among biomarkers, EndoPAT-RHI and organ involvement in patients with SSc. Our data suggest a complex pathological progression of SSc through fibrotic impairment and microvascular damage.