CD13-SPECIFIC AUTOIMMUNITY IN CYTOMEGALOVIRUS-INFECTED IMMUNOCOMPROMISED PATIENTS1

Abstract

Cytomegalovirus (CMV) infection has been suggested to be associated with various autoimmune manifestations, such as hemolytic anemia, granulocytopenia, and the formation of autoantibodies. Earlier we found that CMV is associated with a human protein, CD13 (aminopeptidase N), emanating from CMV-infected cells and serving an important function during CMV infection of susceptible cells. We hypothesized that CD13 might become immunogenic if presented to the immune system as a part of the CMV virion. The presence of CD13-specific antibodies was tested using a microcytotoxicity assay against CD13-positive human monocytes, or by flow cytometric assays against mouse cells transfected with human CD13; specificity was assessed by specific blocking with monoclonal antibodies. CD13 reactivity was also demonstrated in immunoprecipitation experiments. CD13-specific antibodies were identified in 15 of 33 bone marrow transplant patients, but exclusively in patients who had experienced either CMV disease (9/10) or CMV viremia (6/9), and appeared at the time of CMV detection. None of the remaining 14 patients without signs of CMV infection were positive for CD13 antibodies(P