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Circulation. 1997;96:1605-1611

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*Heart Transplantation

(Circulation. 1997;96:1605-1611.)
© 1997 American Heart Association, Inc.


Articles

Major Histocompatibility Complex Class II Antigen Expression in Rejecting Cardiac Allografts

Detection Using In Vivo Imaging With Radiolabeled Monoclonal Antibody

A. Iain McGhie, MD; Branislav Radovancevic, MD; Pavel Capek, MD; Warren H. Moore, MD; Leela Kasi, PhD; Lamk Lamki, MD; Fred J. Clubb, Jr, DVM, PhD; O. Howard Frazier, MD; ; James T. Willerson, MD

From the University of Texas– Houston Medical School (A.I.M., L.L., O.H.F., J.T.W.), Texas Heart Institute/St Luke's Episcopal Hospital (B.R., P.C., F.J.C., O.H.F., J.T.W.), and Baylor College of Medicine (W.H.M.), Houston, Tex.

Correspondence to A. Iain McGhie, MD, University of Texas– Houston Medical School, Department of Internal Medicine (Cardiology Division), 6431 Fannin, Room 1.228 MSB, Houston, TX 77225. E-mail mcghie{at}heart.med.uth.tmc.edu

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 (131I [n=2], 123I [n=1], or 111In [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 111In-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 111In-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.


Key Words: transplantation • rejection • radioisotopes • imaging • immunology




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