CORRELATION OF INTERSTITIAL PNEUMONIA WITH HUMAN CYTOMEGALOVIRUS-INDUCED LUNG INFECTION AND GRAFT-VERSUS-HOST DISEASE AFTER BONE-MARROW TRANSPLANTATION

In a retrospective analysis lung biopsy specimens obtained postmortem from 30 consecutive allogeneic bone marrow transplant recipients who h ad died of either interstitial pneumonitis (IP; 18/30 patients) or var ious other causes (12/30 patients) were studied for the local presence of human cytomegalovirus (HCMV) by culture, in situ hybridization, po lymerase chain reaction (PCR) and immunohistochemistry for HCMV protei ns. All patients suffering from IP were found to be HCMV positive in t he lung biopsy. PCR revealed the highest sensitivity for HCMV detectio n in lung biopsies, but in 15/18 PCR-positive samples local HCMV infec tion could be confirmed by at least one additional technique. All the lung biopsies obtained from the 12 patients without IP were negative f or HCMV by all techniques applied, except one with a weak HCMV-DNA sig nal in the PCR assay. The severity of the clinical, as well as histolo gical and immunohistological alterations in the lung did not correlate with the amount of HCMV-DNA or the number of HCMV-positive cells dete cted in the biopsy. An increase of HLA-class II antigen and of ICAM-1 expression on the alveolar epithelium, as well as presence of activate d CD8(+) or CD4(+) lymphocytes infiltrating only HCMV-positive lung bi opsies 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 HC MV appears to be the primary requirement for the initiation of IP. GvH D, however, may interfere with normal control of subsequent antiviral immune responses and, thus, provoke the immunopathology of IP.