Serum thymus and activation regulated chemokine levels post-lung transplantation as a predictor for the bronchiolitis obliterans syndrome

Abstract

SummaryThe main reason for mortality after lung transplantation is the bronchiolitis obliterans syndrome (BOS), which represents chronic rejection. As soluble CD30, which is produced mainly by activated T helper 2 (Th2) cells, was shown to be related to development of BOS, we aimed to investigate the relation between development of BOS and Th2 chemoattractant thymus and activation regulated chemokine (TARC/CCL17). In 54 patients we measured serum TARC levels prior to transplantation by enzyme-linked immunosorbent assay, and in 44 of these patients sera were analysed at months 1, 2 and 3 after lung transplantation. In addition, longitudinal measurements were performed in sera from eight healthy controls and 14 patients, the latter taken over a period of 2 years post-transplantation from seven patients developing BOS plus seven clinically matched BOS-free patients. Median serum TARC levels post-transplantation of patients who developed BOS were significantly lower than those of the matched BOS-free patients (P = 0·05). A receiver operating characteristics analysis (area under the curve 0·77), together with a Kaplan-Meyer analysis, showed that serum TARC levels below 325 pg/ml in the first month post-transplantation can predict development of BOS post-transplantation (P = 0·001). In contrast, pretransplant serum TARC levels were not significantly different between patients developing BOS, BOSfree patients or healthy controls. In conclusion, pretransplantation serum TARC levels do not predict the development of BOS post-transplantation, but measurement of the serum TARC levels in the first month directly after transplantation can provide us with a tool to identify the group at risk of developing BOS.

Systemic and exhaled cytokine and chemokine profiles are associated with the development of bronchiolitis obliterans syndrome

“…37 In animal models, IL-13 prolongs graft rejection in heart allografts. 38 The findings of reduced concentrations of IL-4 and IL-13 in BOS pos patients compared with BOS neg patients are in concert with the results of Paantjens et al 39 They found that median serum Th2 chemoattractant thymus and activationregulated chemokine levels were significantly lower in BOS pos patients than in BOS neg patients.…”

Lung transplantation affects expression of the chemokine receptor type 4 on specific T cell subsets

“…Blood-borne Tregs preferentially express both CCR4 and CCR8, but as mature dendritic cells (DCs) produce TARC and MDC and almost no CCR8 chemokines, the main route of Treg attraction is via CCR4 [15]. This supports the hypothesis that decreased levels of TARC produced by mature DC in the lungs at time of inflammation would result in reduced attraction of Tregs, thereby contributing to ongoing inflammation leading to BOS development [3].…”

“…TARC, MCP‐1 and MDC have all been studied in relation to the development of BOS. Concentrations of TARC present in the circulation 1 month after LTx were decreased in patients who eventually developed BOS [3]. MCP‐1 was elevated prior to BOS [4], while high MDC levels in BALF at 6 months post‐transplantation were speculated to be predictive for BOS development [5,6].…”

Chronic Allograft Rejection: Epidemiology, Diagnosis, Pathogenesis, and Treatment

“…In one study blood CD4þ CD25þ high regulatory T cells were lower in patients with BOS compared with stable lung transplant recipients. 123 In other studies, elevated levels of soluble CD30, 124 elevated thymus and activation regulated chemokine (TARC)/ CCL17, 125 and decreased clara cell secretory protein (CC16) in the blood were associated with BOS. 126 …”