Is Combined Pretransplantation Seropositivity of Kidney Transplant Recipients for Cytomegalovirus Antigens (pp150 and pp28) a Predictor for Protection against Infection?

The records of 545 patients were reviewed for risk factors associated with cytomegalovirus (CMV) infection after marrow transplant. CMV infection occurred among 36% of seronegative patients and 69% of seropositive patients. Among seronegative patients, significant risk factors for CMV infection included positive serology of the marrow donor (relative rate, 2.3) and the use of granulocyte transfusions from seropositive donors (relative rate, 2.5). Among both seronegative and seropositive patients, the occurrence of acute graft-versus-host disease (GVHD) significantly increased the risk of CMV infection (average relative rate, 1.8) and of subsequent CMV pneumonia (average relative rate, 2.6). CMV excretion and viremia were each associated with subsequent pneumonia, but the positive predictive values were low. One-third of long-term survivors excreted CMV at greater than 250 days after transplantation. The only risk factor for late excretion was CMV infection that occurred in the first 150 days after transplantation. In contrast to the effect of acute GVHD on CMV infection, CMV infection did not increase the risk of either acute or chronic GVHD.

Human cytomegalovirus (HCMV)-specific antibody responses after primary maternal infection were examined to determine if specific deficits in antibody response were associated with intrauterine transmission. Anti-glycoprotein B IgG antibodies were significantly higher at delivery in transmitters than in nontransmitters, suggesting that the amount of antiviral antibody was not reflective of protection from transmission. Characterization of the qualitative antibody response revealed lower neutralizing antibody titers in transmitters, suggesting an association between neutralizing activity and intrauterine transmission. Examination of anti-HCMV antibody avidity revealed that the majority of nontransmitters but 2.0 (P < .002). A significant correlation between neutralizing titers and antibody avidity was demonstrated. Thus, antibody affinity maturation is critical for production of high levels of neutralizing antibodies during primary HCMV infection, and a defect in affinity maturation may play a role in intrauterine transmission of HCMV.

Virus shedding from the epithelial cells of the serous acini of salivary glands is a major source for the horizontal transmission of cytomegalovirus. These cells are, different to other tissues, exempt from CD8 T lymphocyte control. CD4 T lymphocytes are essential to terminate the productive infection. Here, we prove that T-B cooperation and the production of antibodies are not required for this process. For the infection with murine cytomegalovirus, mutant mice were used which do not produce antibodies because of a disrupted membrane exon of the immunoglobulin mu chain gene. Also, in these mice the virus clearance from salivary glands is a function of CD4 T lymphocytes. However, these mice clear the virus and establish viral latency with a kinetics that is distinguishable from normal mice. Reactivation from virus latency is the only stage at which the absence of antibodies alters the phenotype of infection. In immunoglobulin-deficient mice, virus recurrence results in higher virus titers. The adoptive serum transfer proved that antibody is the limited factor that prevents virus dissemination in the immunodeficient host.