Background: Human and animal studies of acute allograft rejection have implicated CCR5 and CXCR3 chemokines as causative factors. However these chemokines have not been assessed in transplant coronary artery disease (TCAD).
Methods and results: Serum levels of chemokines were measured by ELISA. Levels of ITAC/CXCL11 were found to be elevated in patients with severe TCAD compared with long-term survivors of transplantation without TCAD and with healthy volunteers who had not undergone transplantation (1.476+/-0.274 ng/mL, 0.926+/-0.466 ng/mL, and 0.741+/-0.321 ng/mL, respectively; P<0.05 for all comparisons to TCAD group). Immunohistochemical localization confirmed the presence of CXCR3+ mononuclear cells within lesions and the presence of the ligand, ITAC/CXCL11, on the surface of endothelial cells associated with TCAD.
Conclusions: Elevated peripheral blood levels of the CXCR3 chemokine ITAC/CXCL11 are associated with severe TCAD and may serve as a marker for patients at increased risk for the development of this disease. Immunohistochemical localization of the CXCR3 chemokine ligand ITAC/CXCL11 on the endothelial surface of TCAD lesions with underlying infiltration of inflammatory mononuclear cells expressing CXCR3 suggests a causative role for this chemokine in the development of TCAD. The present study is one of the first to demonstrate a role for ITAC/CXCL11 in this disease.