title: 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.
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. rupal.shah@uphs.upenn.edu
authors.forename: Rupal J
authors.initials: RJ
authors.lastname: Shah
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Diamond
authors.forename: David J
authors.initials: DJ
authors.lastname: Lederer
authors.forename: Selim M
authors.initials: SM
authors.lastname: Arcasoy
authors.forename: Edward M
authors.initials: EM
authors.lastname: Cantu
authors.forename: E J
authors.initials: EJ
authors.lastname: Demissie
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kohl
authors.forename: James C
authors.initials: JC
authors.lastname: Lee
authors.forename: Joshua
authors.initials: J
authors.lastname: Sonett
authors.forename: Jason D
authors.initials: JD
authors.lastname: Christie
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D055031:Primary Graft Dysfunction / Q000097:blood*; D011446:Prospective Studies; D012121:Respiration, Artificial; D013997:Time Factors
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2