Dataset Information

Plasma monocyte chemotactic protein-1 levels at 24 hours are a biomarker of primary graft dysfunction after lung transplantation.

ABSTRACT: Monocyte chemotactic protein-1 (MCP-1), also known as "chemokine ligand 2" (CCL2), is a monocyte-attracting chemokine produced in lung epithelial cells. We previously reported an association of increased levels of plasma MCP-1 with primary graft dysfunction (PGD) after lung transplantation in a nested case-control study of extreme phenotypes using a multiplex platform. In this study, we sought to evaluate the role of plasma MCP-1 level as a biomarker across the full spectrum of PGD. We performed a prospective cohort study of 108 lung transplant recipients within the Lung Transplant Outcomes Group cohort. Plasma MCP-1 levels were measured pretransplantation and 6 and 24 hours after transplantation. The primary outcome was development of grade 3 PGD within 72 hours of transplant, with secondary analyses at the 72-hour time point. Multivariable logistic regression was used to evaluate confounding. Thirty subjects (28%) developed PGD. Median MCP-1 measured at 24 hours post-transplant was elevated in subjects with PGD (167.95 vs 103.5 pg/mL, P = .04). MCP-1 levels at 24 hours were associated with increased odds of grade 3 PGD after lung transplantation (odds ratio for each 100 pg/mL, 1.24; 95% confidence interval, 1.00-1.53) and with grade 3 PGD present at the 72-hour time point (odds ratio for each 100 pg/mL, 1.57; 95% confidence interval, 1.18-2.08), independent of confounding variables in multivariable analyses. MCP-1 levels measured preoperatively and 6 hours after transplant were not significantly associated with PGD. Persistent elevations in MCP-1 levels at 24 hours are a biomarker of grade 3 PGD post-transplantation. Monocyte chemotaxis may play a role in the pathogenesis of PGD.

SUBMITTER: Shah RJ

PROVIDER: S-EPMC3500407 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Plasma monocyte chemotactic protein-1 levels at 24 hours are a biomarker of primary graft dysfunction after lung transplantation.

Shah Rupal J RJ Diamond Joshua M JM Lederer David J DJ Arcasoy Selim M SM Cantu Edward M EM Demissie E J EJ Kawut Steven M SM Kohl Benjamin B Lee James C JC Sonett Joshua J Christie Jason D JD Ware Lorraine B LB

Translational research : the journal of laboratory and clinical medicine 20120916 6

Monocyte chemotactic protein-1 (MCP-1), also known as "chemokine ligand 2" (CCL2), is a monocyte-attracting chemokine produced in lung epithelial cells. We previously reported an association of increased levels of plasma MCP-1 with primary graft dysfunction (PGD) after lung transplantation in a nested case-control study of extreme phenotypes using a multiplex platform. In this study, we sought to evaluate the role of plasma MCP-1 level as a biomarker across the full spectrum of PGD. We performed ...[more]

PMID: 22989614

Similar Datasets

Project description:The clinical use of circulating biomarkers for primary graft dysfunction (PGD) after lung transplantation has been limited. In a prospective single-center cohort, we examined the use of plasma protein biomarkers as indicators of PGD severity and duration after lung transplantation. The study comprised 40 consecutive lung transplant patients who consented to blood sample collection immediately pretransplant and at 6, 24, 48, and 72 h after lung transplant. An expert grader determined the severity and duration of PGD and scored PGD at T0 (6 h after reperfusion), T24, T48, and T72 h post-reperfusion using the 2016 ISHLT consensus guidelines. A bead-based multiplex assay was used to measure 27 plasma proteins including cytokines, growth factors, and chemokines. Enzyme-linked immunoassay was used to measure cell injury markers including M30, M65, soluble receptor of advanced glycation end-products (sRAGE), and plasminogen activator inhibitor-1 (PAI-1). A pairwise comparisons analysis was used to assess differences in protein levels between PGD severity scores (1, 2, and 3) at T0, T24, T48, and T72 h. Sensitivity and temporal analyses were used to explore the association of protein expression patterns and PGD3 at T48-72 h (the most severe, persistent form of PGD). We used the Benjamini-Hochberg method to adjust for multiple testing. Of the 40 patients, 22 (55%) had PGD3 at some point post-transplant from T0 to T72 h; 12 (30%) had PGD3 at T48-72 h. In the pairwise comparison, we identified a robust plasma protein expression signature for PGD severity. In the sensitivity analysis, using a linear model for microarray data, we found that differential perioperative expression of IP-10, MIP1B, RANTES, IL-8, IL-1Ra, G-CSF, and PDGF-BB correlated with PGD3 development at T48-72 h (FDR < 0.1 and p < 0.05). In the temporal analysis, using linear mixed modeling with overlap weighting, we identified unique protein patterns in patients who did or did not develop PGD3 at T48-72 h. Our findings suggest that unique inflammatory protein expression patterns may be informative of PGD severity and duration. PGD biomarker panels may improve early detection of PGD, predict its clinical course, and help monitor treatment efficacy in the current era of lung transplantation.

Project description:PurposeClinical models to identify patients at high risk of primary graft dysfunction (PGD) after heart transplantation (HT) are limited, and the underlying pathophysiology of this common post-transplant complication remains poorly understood. We sought to identify whether pre-transplant levels of circulating proteins reporting on immune activation and inflammation are associated with incident PGD.MethodsThe study population consisted of 219 adult heart transplant recipients identified between 2016 and 2020 at Duke University Medical Center, randomly divided into derivation (n = 131) and validation (n = 88) sets. PGD was defined using modified ISHLT criteria. Proteomic profiling was performed using Olink panels (n = 354 proteins) with serum samples collected immediately prior to transplantation. Association between normalized relative protein expression and PGD was tested using univariate and multivariable (recipient age, creatinine, mechanical circulatory support, and sex; donor age; ischemic time) models. Significant proteins identified in the derivation set (p < 0.05 in univariate models), were then tested in the validation set. Pathway enrichment analysis was used to test candidate biological processes. The predictive performance of proteins was compared to that of the RADIAL score.ResultsNine proteins were associated with PGD in univariate models in the derivation set. Of these, only CLEC4C remained associated with PGD in the validation set after Bonferroni correction (OR [95% CI] = 3.04 [1.74,5.82], p = 2.8 × 10-4). Patterns of association were consistent for CLEC4C in analyses stratified by biventricular/left ventricular and isolated right ventricular PGD. Pathway analysis identified interferon-alpha response and C-type lectin signaling as significantly enriched biologic processes. The RADIAL score was a poor predictor of PGD (AUC = 0.55). CLEC4C alone (AUC = 0.66, p = 0.048) and in combination with the clinical covariates from the multivariable model (AUC = 0.69, p = 0.018) improved discrimination for the primary outcome.ConclusionsPre-transplantation circulating levels of CLEC4C, a protein marker of plasmacytoid dendritic cells (pDCs), may identify HT recipients at risk for PGD. Further studies are needed to better understand the potential role pDCs and the innate immune response in PGD.

Project description:BackgroundSeptic cardiomyopathy was recognized more than 30 years ago, but the early phase remains uncharacterized as no existing studies captured patients at the time of Emergency Department (ED) presentation, prior to resuscitation. Therapeutic interventions alter cardiac function, thereby distorting the relationship with disease severity and outcomes. The goal of this study was to assess the impact of illness severity on cardiac function during the first 24 h of sepsis admission.MethodsThis was a pre-planned secondary analysis of a prospective observational study of adults presenting to the ED with suspected sepsis (treatment for infection plus either lactate > 2 mmol/liter or systolic blood pressure < 90 mm/Hg) who received < 1L IV fluid before enrollment. Patients had 3 echocardiograms performed (presentation, 3, and 24 h). The primary outcome was the effect of increasing sepsis illness severity, defined by ED Sequential Organ Failure Assessment (SOFA) score, on parameters of cardiac function, assessed using linear mixed-effects models. The secondary goal was to determine whether cardiac function differed between survivors and non-survivors, also using mixed-effects models.ResultsWe enrolled 73 patients with a mean age of 60 (SD 16.1) years and in-hospital mortality of 23%. For the primary analysis, we found that increasing ED SOFA score was associated with worse cardiac function over the first 24 h across all assessed parameters of left-ventricular systolic and diastolic function as well as right-ventricular systolic function. While baseline strain and E/e' were better in survivors, in the mixed models analysis, the trajectory of Global Longitudinal Strain and septal E/e' over the first 24 h of illness differed between survivors and non-survivors, with improved function at 24 h in non-survivors.ConclusionsIn the first study to capture patients prior to the initiation of resuscitation, we found a direct relationship between sepsis severity and global myocardial dysfunction. Future studies are needed to confirm these results, to identify myocardial depressants, and to investigate the link with adverse outcomes so that therapeutic interventions can be developed.

Dataset Information

Plasma monocyte chemotactic protein-1 levels at 24 hours are a biomarker of primary graft dysfunction after lung transplantation.

Publications

Plasma monocyte chemotactic protein-1 levels at 24 hours are a biomarker of primary graft dysfunction after lung transplantation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets