Cellular and humoral cytomegalovirus immunity changes in one-year combined prophylaxis after lung transplantation: suggestions from and for clinical practice

Background: Immune responses, both cellular and humoral, against cytomegalovirus (CMV) are used to predict CMV manifestations in solid organ recipients. The aim of this study is to evaluate CMV enzyme-linked immunospot (ELISPOT) assay and serology during CMV infections, their concordance and variations after lung transplantation (LTx). Methods: We retrospectively analysed in one year the follow-up data of 43 patients receiving combined CMV prophylaxis with antiviral agents and CMV-specific immunoglobulin G (IgG). CMV infections were investigated by using molecular analyses on both 167 bronchoalveolar lavage and biopsy specimens and 1134 blood samples. Cellular CMV immunity was assessed with specific ELISPOT whereas the humoral one was assessed by quantifying specific immunoglobulins. Results: At the first month after LTx the majority of patients were ELISPOT responders (52.3%) and 30.9% were non-responders. ELISPOT responders had a lower incidence of CMV viremia (p = 0.047), whereas neither effects on CMV pulmonary asymptomatic infection nor on acute rejection were observed. Responders had a higher CMV IgG titre (p < 0.0001) in particular at the first month after LTx (p = 0.0001). Concordance among CMV ELISPOT assay and IgG levels was moderate (Cohen’s K 0.524), with an agreement of 89.8%. All ELISPOT responders maintained their status and almost all non-responders became responders during follow-up (92.3%); the percentage of IgG seropositive subjects increased from 74.4% at the first month of follow-up to 97.4% after 1 year. Conclusions: Despite a moderate concordance with serology, ELISPOT response predicted a lower incidence of CMV viremia in LTx patients; no effects were reported on pulmonary clinical manifestations nor on acute rejection. The ELISPOT response as well as serology changed during the follow-up, not only after first CMV contact. The reviews of this paper are available via the supplemental material section.