Major Histocompatibility Complex Class II Antigen Expression in Rejecting Cardiac Allografts

Abstract

Background Increased expression of major histocompatibility complex class II (MHC-II) antigen occurs during cardiac allograft rejection. We tested the hypotheses that (1) radiolabeled antibody to MHC-II antigen allows detection of cardiac allograft rejection using nuclear imaging techniques and (2) uptake of radiolabeled antibody to MHC-II antigen correlates with severity of rejection. Methods and Results Thirteen beagles with cervical cardiac allografts were studied for 64±23 days by use of myocardial biopsy and in vivo imaging. Uptake of radiolabeled ( 131 I [n=2], 123 I [n=1], or 111 In [n=10]) antibody to MHC-II increased over baseline in 7 animals that developed histological evidence of progressively worsening allograft rejection (group A), from 72.2±46.1 to 176.8±102.0 counts/pixel/mCi ( P <.009). In 4 beagles without progressively worsening allograft rejection (group B), uptake was unchanged during follow-up (74.4±43.8 and 60.2±37.4 counts/pixel/mCi; P =NS). In animals studied with 111 In-labeled antibody, uptake increased from 102.9±23.1 at baseline to 233.2±82.7 counts/pixel/mCi at follow-up in group A animals ( P =.036), with no significant change in group B (91.1±34.9 and 75.9±24.9 counts/pixel/mCi; P =NS). Uptake of 111 In-labeled antibody was 107.5±35.7, 135.9±70.8, and 307.8±90.1 counts/pixel/mCi in biopsy samples showing evidence of mild, moderate, and severe rejection, respectively ( P =.001). Biopsy samples showing mild, moderate, and intense MHC-II expression antibody uptake had uptakes of 92.6±36.3, 158.5±54.7, and 307.8±90.1 counts/pixel/mCi, respectively ( P =.00004). Conclusions Radiolabeled monoclonal antibodies to MHC-II antigen can detect cardiac allograft rejection in this large mammal model of cardiac allograft transplantation, and this technique may have a potential role in the detection of rejection in patients after cardiac transplantation.