Distinctions between cytomegalovirus-related graft loss and rejection

In reviewing our laboratory findings on renal transplant recipients with active CMV infections, we have uncovered some previously unappreciated associations. First, in contrast with some reports, our patients treated with CsA did not have a lower incidence of CMV infection than the patients treated with Aza plus steroids, but this may be due to the low incidence of CMV we have experienced with the use of low-dose steroids. Moreover, we have found that CsA treatment may inhibit the production of IgM antibodies to a secondary CMV infection and therefore make such infections more difficult to detect without frequent cultures. Secondly, the frequency of graft loss associated with CMV infection was lower in CsA-treated patients. Whether this is related to the altered immune responses to CMV by CsA treatment remains to be investigated. Finally, in our patients, graft loss during active CMV infection occurred more frequently in HLA-DR3 or -7-positive patients and was associated with circulating IgM immune complexes with RF activity and broad leukocytotoxic activity to T lymphocytes, B lymphocytes, granulocytes, and monocytes, whereas graft rejection in the absence of active CMV infection occurred more frequently in DRn6-positive patients and was associated with the production of IgG antibodies to B lymphocytes and monocytes. The time of graft loss also differed between these two groups. Patients with active CMV infections usually lost their grafts between two to five months after transplantation whereas the majority of those without active CMV infection rejected their grafts in less than two months.