Enhanced pretransplant innate immunity predicts rejection in primate vascular allografts: An infectious etiology?

Abstract

Introduction. We previously reported that elevated pretransplant serum C-reactive protein (CRP) predicts increased posttransplant vascular rejection in a primate arterial allograft model. In the current study, we examined peritransplant behavior of serum neopterin in these CMV+ primates to determine its reliability as a marker of innate immune responsiveness in a transplant setting. We also investigated a possible link between systemic inflammation, innate immunity, and peritransplant CMV activity. Methods. Allograft recipient serum neopterin was measured weekly for 4 weeks, both before and immediately after transplantation, and compared to serum CRP measured over the same period. Pretransplant levels of both markers were compared to pretransplant oral and genital CMV shedding, as measured by PCR over a 2-month period. Allografts explanted 6 weeks after transplantation were also analyzed by PCR for evidence of CMV. Results. High CRP animals had higher mean levels of pretransplant neopterin then did their low CRP counterparts (6.04 ± 1.93 versus 3.56 ± 1.09 mg/dl, P = 0.030). These high CRP/neopterin animals had more chronic vascular rejection after 6 weeks. While CRP varied widely after transplantation, neopterin remained largely unchanged from pretransplant levels: 6.96 ± 2.54 and 3.48 ± 0.96 mg/dl at 1-week posttransplant, for high and low CRP animals, respectively ( P = 0.002). Neither CRP nor neopterin levels correlated with pretransplant CMV shedding; however, evidence of CMV in the allograft was only found in high CRP/neopterin animals. Conclusions. Occult systemic inflammation and innate immune activity correlate in healthy pretransplant primates and may predict risk for rejection after allograft transplantation. While CRP levels appear to be altered significantly by an operative transplant procedure, neopterin levels do not, suggesting that neopterin may still be a reliable marker of innate immune activity even in the early posttransplant period. Pretransplant CMV shedding does not appear to influence systemic inflammation or innate immune responsiveness; however, allografts in high CRP/neopterin recipients may attract CMV.