Laboratory-clinical correlates of time-associated lesions in the vascular immunopathology of human cardiac allografts.
Ninety cardiac allograft recipients were studied for clinical and functional parameters during a 40-month period. Baseline histologic and immunocytochemical data were obtained from donors' hearts before transplantation, and serial endomyocardial biopsy specimens were studied histologically for cellular infiltrates and immunocytochemically for complement and immunoglobulin deposits and for components of the hemostatic, fibrinolytic, and natural anticoagulant pathways. Results were grouped according to the time from transplantation: the first 3 months, 4 to 21 months, and 22 to 40 months. Each group was evaluated for most frequently obtained immunocytochemical findings and results relevant to clinical-laboratory cooperation in patient management. During the first 3 months, findings of biopsy specimens from allografts that subsequently were going to be problem cases revealed depleted tissue plasminogen activator in arteriolar smooth muscle cells, and recipient IgM that was deposited on donor endothelium of stable grafts was diminished or absent in unstable allografts. In addition, vascular deposits of activated complement components were identified in 50 of 70 allografts. From 4 through 21 months after transplantation, vascular deposits of complement rarely were identified (even in patients who previously had positive biopsy specimens), and the principal vascular lesion was fibrin deposits with impaired anticoagulant pathways and inadequate fibrinolysis, usually without associated cellular infiltrates. From 22 through 40 months after transplantation, the principal vascular lesion was graft-induced atherosclerosis. These immunocytochemically defined qualitative and quantitative changes in unstable or failing allografts form a time-related spectrum of lesions that encompasses the emerging diagnostic entity of vascular rejection.
Faulk
W P
WP
Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, Indianapolis 46202.
Labarrere
C A
CA
Pitts
D
D
Halbrook
H
H
D001706:Biopsy; D003165:Complement System Proteins / Q000032:analysis; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology*; D005260:Female; D005337:Fibrin / Q000032:analysis; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000032:analysis
D007075:Immunoglobulin M; D005337:Fibrin; D003165:Complement System Proteins; D010959:Tissue Plasminogen Activator