Patterns of myocardial cell adhesion molecule expression in human endomyocardial biopsies after cardiac transplantation. Induced ICAM-1 and VCAM-1 related to implantation and rejection.
Conflicting patterns of myocardial cell adhesion molecule expression associated with cardiac rejection have emerged from numerous studies of randomly selected cardiac biopsies. We designed a prospective, longitudinal study which reports both qualitative and quantitative levels of myocardial ICAM-1, VCAM-1, E-selectin, and P-selectin expression in sequential human cardiac allograft biopsies. Intense ICAM-1 and VCAM-1 staining was found in all biopsies during the first three weeks after transplant and coincided with elevated serum levels of troponin T, a sensitive marker of ischemic myocyte injury. Baseline ICAM-1 and VCAM-1 expression returned within three to four weeks, as did serum troponin T levels in all patients who did not develop rejection. All 29 rejection episodes encountered were associated with intense ICAM-1 staining, while 24 of the 29 (83%) had intense VCAM-1 staining. Increased ELAM-1 and CD62 staining was only rarely observed. Persistence of increased ICAM-1 and VCAM-1 staining after treated rejection episodes predicted a recurrent rejection episode within two months (75% positive and 100% negative predictive value). Objective quantitative measurements by radioimmunoassay (RIA) confirmed these patterns of induced ICAM-1 and VCAM-1 expression. Thus, longitudinal monitoring of serial biopsies for myocardial ICAM-1 and VCAM-1 expression could be useful in the early detection of rejection episodes and monitoring the efficacy of immunosuppressive therapy.
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205.
A
A
Herskowitz
A E
AE
Mayne
S B
SB
Willoughby
K
K
Kanter
A A
AA
Ansari
D000328:Adult; D015415:Biomarkers; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000032:analysis*; D003402:Creatine Kinase / Q000097:blood; D004699:Endocardium / Q000276:immunology / Q000473:pathology; D006084:Graft Rejection / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008137:Longitudinal Studies; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D011446:Prospective Studies; D014184:Transplantation, Homologous; D014336:Troponin / Q000097:blood; D020107:Troponin T
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D007527:Isoenzymes; D014336:Troponin; D020107:Troponin T; D003402:Creatine Kinase