Serum Adhesion Molecule Levels as Prognostic Markers in Patients with Early Systemic Sclerosis: A Multicentre, Prospective, Observational Study

Minoru Hasegawa,Kazuhiko Takehara,Daisuke Goto,Hirahito Endo,Katsumi Inoue,Masataka Kuwana,Sumiaki Tanaka,Yoshihide Asano,Manabu Fujimoto,Shinichi Sato,Hiroki Takahashi,Hironobu Ihn,Osamu Ishikawa,Fumihide Ogawa,Yasushi Kawaguchi

doi:10.1371/journal.pone.0088150

Abstract

ObjectiveTo assess the utility of circulating adhesion molecule levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease.MethodsNinety-two Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicentre, observational study. Concentrations of intercellular adhesion molecule (ICAM) −1, E-selectin, L-selectin, and P-selectin in serum samples from all patients were measured by enzyme-linked immunosorbent asssay (ELISA). In 39 patients, adhesion molecule levels were measured each year for four years. The ability of baseline adhesion molecule levels to predict subsequent progression and severity in clinical and laboratory features were evaluated statistically.ResultsAt their first visit, serum levels of ICAM-1, E-selection, P-selectin were significantly elevated and serum L-selectin levels were significantly reduced in patients with SSc compared with healthy controls. Overall, serum ICAM-1 levels at each time point were significantly inversely associated with the %vital capacity (VC) of the same time and subsequent years by univariate analysis. The initial serum ICAM-1 levels were significantly inversely associated with the %VC at the fourth year by multiple regression analysis. The initial serum P-selectin levels were significantly associated with the health assessment questionnaire disability index (HAQ-DI) at the fourth year by multiple regression analysis. Initial adhesion molecule levels were not significantly associated with other clinical features including skin thickness score. Baseline adhesion molecule levels were not significantly associated with subsequent rate of change of clinical parameters.ConclusionIn patients with SSc, serum levels of ICAM-1 and P-selectin may serve as prognostic indicators of respiratory dysfunction and physical disability, respectively. Further longitudinal studies of larger populations are needed to confirm these findings.

Highlights

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis in the skin and internal organs, and vascular involvement [1,2]
Serum levels of intercellular adhesion molecule (ICAM)-1 were significantly increased in systemic sclerosis (SSc) patients compared with healthy controls (p,0.0001, Figure 1)
Serum levels of E-selectin and P-selectin were significantly elevated in the SSc patients (p, 0.01 vs. p,0.0001, respectively, Figure 1)

Summary

Introduction

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis in the skin and internal organs, and vascular involvement [1,2]. Interstitial lung disease (ILD) develops in more than half of SSc patients and is one of the major SSc-related causes of death. Joint contracture due to extensive skin sclerosis and/or severe internal organ involvement results in impaired physical function. SSc patients exhibit increased numbers and activation of monocytes/macrophages and T cells in the circulation and tissues [3,4]. Infiltration of these cells into the skin or internal organs may promote endothelial damage and fibrosis, most likely through the production of soluble mediators including cytokines and chemokines. Leukocyte recruitment into inflammatory sites is generally achieved using multiple cell adhesion molecules [5]

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Conclusion