Three Sensitive Methods for the Detection of Cytomegalovirus in Lung Tissue of Patients with Interstitial Pneumonitis

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Abstract
Interstitial pneumonia after allogeneic bone marrow transplantation is frequently associated with human cytomegalovirus (HCMV) infection. However, in a considerable proportion of the cases, no infectious agent can be determined and the interstitial pneumonia is then classified as idiopathic. Hypothetically, idiopathic interstitial pneumonia could be caused by HCMV present in such small amounts or such conformation that the virus cannot be detected by routine histopathologic analysis or viral culture techniques. To check this hypothesis, three sensitive methods for HCMV detection (in situ hybridization, the polymerase chain reaction for HCMV-DNA detection, and immunohistochemistry for the detection of HCMV immediate early antigens) have been applied on lung tissue sections of bone marrow transplant patients who died with interstitial pneumonia. Three categories were distinguished: (1) patients with HCMVrelated interstitial pneumonia (n = 5); (2) patients with idiopathic interstitial pneumonia (n = 10); and (3) patients with HCMV interstitial pneumonia who had been treated with antiviral therapy (n = 2). In the first category, all three techniques yielded clearly positive results, whereas these techniques indicated that one of the patients of the second category had HCMV-related pneumonia. In the third category no positive signals could beobtained. The presented data indicate that a direct involvement of HCMV in idiopathic interstitial pneumonia is unlikely. However, a PCR performed for Epstein-Barr virus (EBV) was positive in two patients with idiopathic interstitial pneumonia. These data indicate that the introduction of new sensitive techniques such as in situ hybridization, immunohistochemistry, and the polymerase chain reaction revives the interest for HCMV and other causative infectious agents in idiopathic interstitial pneumonia.