Human cytomegalovirus and acute rejection after heart transplantation are not directly associated

Abstract

Retrospective and prospective analyses of heart transplant recipients showed no significant association between acute rejection and the detection of cytomegalovirus (CMV) infection by culture or the polymerase chain reaction (PCR) for viral DNA, neither on grounds of the incidence of both conditions nor in relation to which was diagnosed first in the patient. Semiquantitative PCR of serial blood and endomyocardial biopsy specimens from individual patients revealed different patterns in the development of the viral DNA in the blood and the heart, also clear episodes of CMV infection in CMV antibody-negative recipients of hearts from CMV antibody-negative donors, none of whom went on to develop a CMV-specific antibody response. None of these findings was associated with the development of rejection in the patient. On the other hand, in those patients who did experience rejection, peak levels of CMV DNA in the blood and the heart were usually not reached until 6 weeks or more after transplantation, whereas in those in whom rejection was not detected at all during the period of observation, peak levels of CMV DNA were detected earlier, mainly within the first 6 weeks after transplantation. In several cases, the delayed increase in CMV DNA in those with rejection, albeit not the delay itself, was linked to treatment with steroids. These findings support the view that CMV infection and rejection are independent events, but that the timing of the infection, and whether or not rejection is detected, are indicative of the general status of the immune response in individual patients.

Viral loads in dual infection with HIV-1 and cytomegalovirus

“…Five children were CMV antibody negative or equivocal, while being weakly positive for CMV DNA. A similar discrepancy between CMV serology and PCR has been noted previously in a group of heart transplant patients 16. Interestingly, this suggests that there might be a qualitative or quantitative effect of immunosuppression on CMV antibody production in some patients.…”

“…The details of the primer sequences, the composition of the PCR reaction mixture, and the cycling conditions were as described previously 1314 The HIV-1 and CMV DNA amplicons were resolved in a 6% mini polyacrylamide gel from which the appropriate specific bands were eluted for direct sequencing15 and for CMV DNA restriction analysis 16. Samples found to be negative by the HIV PCR were retested by PCR against primers specific for the “housekeeping” histidyl tRNA synthetase (HRS) gene14; these primers were not included routinely because the product size (360 bp) was the same as with the HIV env primers.…”

“…The sensitivity of the CMV mtrII PCR was of the order of one copy of specific plasmid DNA,16 as was that of the HIV-1 env PCR13 when determined using the MRC ADP PCR reference reagents set (No. ADP956) 17…”

Long-term outcome of cytomegalovirus high-risk patients after heart transplantation: comparison between two prophylactic regimes – a single-center experience

“…Whether CMV infection can induce acute graft rejection [3,9,22,26] (through increased HLA class II antigen expression) or if intensified immunosuppression early after transplantation and after treatment of rejection predisposes patients to CMV infection [2,19,22,28] is controversially discussed. The striking differences in the incidence of symptomatic CMV infection between recipients of different organs (heart, lung, heart-lung, liver and kidney) have been attributed to different intensive immunosuppression regimes used in these groups [22].…”