Evaluation and significance of cytomegalovirus-specific cellular immune response in lung transplant recipients

Abstract

In lung transplant recipients, cytomegalovirus (CMV) has been associated with direct ie, organ and systemic infection/disease, and indirect effects, including predisposition to develop acute rejection episodes and chronic allograft dysfunction. Cellular immune responses have been demonstrated to play a role in the control of CMV replication. We evaluated CMV-specific cellular responses among lung transplant recipients associated with the onset of organ infection/disease. Cellular responses were evaluated by an Elispot assay of 48 specimens from 24 patients. All samples were evaluated beyond 1 year after transplantation; CMV DNA was concomitantly detected in bronchoalveolar lavage (BAL) and whole blood specimens. Each patient received a combined prolonged antiviral prophylaxis with CMV Ig for 12 months and gancyclovir or valgancyclovir for 3 weeks after postoperative day 21. Nine patients (37.5%) showed transient or persistent CMV nonresponses including donor-recipient negative serologic matching in 2 cases. Positive CMV DNA results were observed in 18/48 BAL specimens (37.5%) from 12 patients (50%). A viral load of >10(4) copies/mL was observed in only 3 cases, 2 of whom were positive also on whole blood. Among these 3 patients, 2 were responders and BAL (as well as whole blood) specimens collected subsequently were negative for CMV DNA; 1 nonresponder patient exhibited a viral load of 426,492 copies/mL BAL (DNAemia, <2,000 copies/mL), developed CMV pneumonia (confirmed by histopathology and immunohistochemistry) and died within 28 days. The prevalence of CMV DNA positivity on BAL did not differ in relation to the immune response; the mean viral load on BAL showed significantly higher results among nonresponders than responders, namely, 1.4 × 10(5) ± 2.4 × 10(5) copies/ml versus 7.9 × 10(3) ± 1.4 × 10(4) (P=.02). Evaluation of CMV-specific cellular immune responses by in vitro immunologic monitoring complements virologic monitoring, helping to identify lung transplant recipients at risk of developing organ infection/disease.