Correlation of interstitial pneumonia with human cytomegalovirus-induced lung infection and graft-versus-host disease after bone marrow transplantation

Abstract

In a retrospective analysis lung biopsy specimens obtained postmortem from 30 consecutive allogeneic bone marrow transplant recipients who had died of either either interstitial pneumonitis (IP; 18/30 patients) or various other causes (12/30 patients) were studied for the local presence of human cytomegalovirus (HCMV) by culture, in situ hybridization, polymerase chain reaction (PCR) and immunohistochemistry for HCMV proteins. All patients suffering from IP were found to be HCMV positive in the lung biopsy. PCR revealed the highest sensitivity for HCMV detection in lung biopsies, but in 15/18 PCR-positive samples local HCMV infection could be confirmed by at least one additional technique. All the lung biopsies obtained from the 12 patients without IP were negative for HCMV by all techniques applied, except one with a weak HCMV-DNA signal in the PCR assay. The severity of the clinical, as well as histological and immunohistological alterations in the lung did not correlate with the amount of HCMV-DNA or the number of HCMV-positive cells detected in the biopsy. An increase of HLA-class II antigen and of ICAM-1 expression on the alveolar epithelium, as well as presence of activated CD8+ or CD4+ lymphocytes infiltrating only HCMV-positive lung biopsies revealed T cell-mediated immune reactions to be involved in the pathogenesis of IP. Since all analyzed patients presented with severe acute or extensive chronic graft-versus-host disease (GvHD), but only those with pulmonary HCMV infection developed IP, dissemination of HCMV appears to be the primary requirement for the initiation of IP. GvHD, however, may interfere with normal control of subsequent antiviral immune response and, thus, provoke the immunopathology of IP.