Cytomegalovirus infection induces anti-endothelial cell antibodies in cardiac and renal allograft recipients.

Cytomegalovirus (CMV) infection represents a significant morbidity factor for transplant recipients. CMV infection has an association with the development of allograft rejection (AR) through graft endothelial cell (EC) damage, but the mechanisms are not yet clear. There are few reports addressing the role of humoral immunity in vascular EC injury mediated by CMV infection whereas many reports are available regarding the mechanism(s) of CMV-associated allograft EC injury mediated by cellular immunity. Here we examine the incidence of CMV infection in 40 cardiac and 25 renal allograft recipients using polymerase chain reaction (PCR) techniques. We also monitored sera for the development of anti-EC antibodies (AECA) using an ELISA with human umbilical vein ECs as targets, and IL-2 levels using an ELISA. AECA levels (immunoglobulin-G and immunoglobulin-M) were significantly elevated in allograft recipients who demonstrated CMV-PCR positivity when compared with the CMV-PCR negative group (IgG: 23.1 +/- 16.4 vs 4.7 +/- 4.5, p < 0.0001; IgM: 47.0 +/- 53.6 vs 7.0 +/- 11.2, p < 0.0001). Serum AECA (IgG and IgM) levels increased one to four weeks after CMV DNA was detected and elevated AECA levels persisted for at least one to two months, and sometimes for several months. Elevated AECA levels correlated well with serum IL-2 levels. These results suggest that CMV infection is associated with an increased humoral immune response to EC antigens, which may be a risk factor for vascular rejection, chronic rejection and decreased allograft survival.