Dataset Information

Clinical Significance of Serum Galectin-9 and Soluble CD155 Levels in Patients with Systemic Sclerosis.

ABSTRACT: Signaling through coinhibitory receptors downregulates the immune response to prevent excessive immune activation and maintain optimal immunity and tolerance. The aim of this study was to examine the levels of the soluble forms of coinhibitory receptors and their ligands, namely, galectin-9 (the ligand of T-cell immunoglobulin and mucin domain 3) and CD155 (the ligand of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain), and their association with clinical features in patients with systemic sclerosis (SSc). The serum levels of galectin-9 and soluble sCD155 were examined by enzyme-linked immunosorbent assays in patients with SSc, and the results were evaluated with respect to clinical features. Patients with SSc exhibited raised serum levels of galectin-9, but not sCD155. Serum galectin-9 levels were raised not only in patients with diffuse cutaneous SSc but also in patients with limited cutaneous SSc. Furthermore, serum galectin-9 levels correlated positively with the erythrocyte sedimentation rate. In addition, increased serum galectin-9 levels tended to be associated with higher mortality and serious organ involvement. These results suggest that galectin-9, but not CD155, may be involved in the pathogenesis of SSc. In addition, the measurement of serum galectin-9 levels could be used to predict serious organ involvement and high mortality in patients with SSc.

SUBMITTER: Chihara M

PROVIDER: S-EPMC6288562 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Clinical Significance of Serum Galectin-9 and Soluble CD155 Levels in Patients with Systemic Sclerosis.

Chihara Mami M Kurita Miki M Yoshihara Yuki Y Asahina Akihiko A Yanaba Koichi K

Journal of immunology research 20181127

Signaling through coinhibitory receptors downregulates the immune response to prevent excessive immune activation and maintain optimal immunity and tolerance. The aim of this study was to examine the levels of the soluble forms of coinhibitory receptors and their ligands, namely, galectin-9 (the ligand of T-cell immunoglobulin and mucin domain 3) and CD155 (the ligand of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain), and their association with clinical features ...[more]

PMID: 30599005

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Project description:BackgroundCD40-CD40 ligand (CD40L) interaction is considered to contribute to the promotion of prothrombotic responses and production of angiogenesis-associated factor in addition to adaptive immune responses. Recently, the role of soluble CD40L (sCD40L) has gained interest in cancer, although its exact functions remain unknown. This study evaluated the clinical significance of sCD40L in patients with pancreatic ductal adenocarcinoma (PDAC) and validated its utility as a PDAC diagnostic and prognostic biomarker.MethodsSerum sCD40L levels were measured by chemiluminescent immunoassay and compared among normal, chronic pancreatitis (CP, high-risk), and PDAC group in both training (n=25 per group) and independent validation (n=30, 30, and 55, respectively) datasets through one-way ANOVA test with the post-hoc Bonferroni method. To evaluate the diagnostic potential of serum sCD40L for PDAC, receiver operating characteristic (ROC) curves were generated and logistic regression analysis was conducted. To investigate the sCD40L-assoicated cytokines/chemokines in PDAC, cytokines/chemokines levels were analyzed by a MILLIPLEX MAP Human Cytokine/Chemokine Kit. To assess the prognostic potentials of sCD40L, Kaplan-Meier survival curve and Cox proportional-hazards regression analysis were applied.ResultsSerum sCD40L levels were significantly higher in PDAC group compared with non-cancer groups in both training (p<0.05) and validation (p<0.05) datasets. Clinically, serum sCD40L closely correlated with unresectability (?s=0.342, p=0.011) and distant metastasis (?s=0.294, p=0.030) of PDAC. ROC curve and logistic regression analysis demonstrated the remarkable predictive potentials of serum sCD40L for PDAC (80.0% sensitivity and 85.5% specificity at cut-off point, 0.45; logistic regression), superior to those of CA19-9 and CEA. According to cytokines/chemokines assay, serum sCD40L levels were closely correlated with serum levels of pro-angiogenic cytokines (EGF, VEGF, IL-8) and immunosuppressive cytokines (IL-6, IL-10, IL-1RA). Kaplan-Meier survival analysis demonstrated patients with high-serum sCD40L (>35,000 ng/ml) had a poorer prognosis than those with low-serum sCD40L (log-rank, p=0.015). Multivariate Cox regression analysis yielded a hazard ratio of 2.509 (95% CI, 1.038-6.067, p=0.041) for mortality in the high-serum sCD40L group.ConclusionsSerum sCD40L is correlated with immunosuppression and angiogenesis in PDAC carcinogenesis/progression, and is a promising diagnostic and prognostic biomarker for PDAC superior to CA19-9 and CEA.

Project description: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.

Dataset Information

Clinical Significance of Serum Galectin-9 and Soluble CD155 Levels in Patients with Systemic Sclerosis.

Publications

Clinical Significance of Serum Galectin-9 and Soluble CD155 Levels in Patients with Systemic Sclerosis.

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