An immunological algorithm to predict risk of high-grade rejection in cardiac transplant recipients.
BACKGROUND
Transplant-related coronary-artery disease (TCAD) develops frequently in cardiac-allograft recipients, and limits long-term survival. We examined the relation between this disorder and cumulative frequency of high-grade rejection, and investigated whether concomitant use of three immunological factors at the time of a low-grade endomyocardial biopsy can predict progression to high-grade rejection.


METHODS
We investigated the relation between the cumulative annual frequency of high-grade rejection and TCAD in 198 recipients of cardiac transplantation between 1992 and 1996 by means of Kaplan-Meier actuarial life-tables. Endomyocardial biopsy, lymphocyte-growth assays, and anti-HLA antibody measurements were compiled over 12 months in 102 patients during their first post-transplant year. We calculated predictive values for high-grade rejection within 90 days by chi2, Kaplan Meier survival curves, and by multivariable logistic regression analyses.


RESULTS
We found a direct correlation between cumulative annual frequency of rejection and TCAD onset with highest risk in those with more than 0.75 rejections per year (p=0.0002). After a low-grade endomyocardial biopsy (0 or 1A), one or more donor-recipient HLA-DR matches protected against high-grade rejections (p<0.001). Among individuals with one or two DR matches, the negative predictive value for progression from a low-grade biopsy to a high-grade rejection was 87% in the presence of a negative lymphocyte-growth assay. Among individuals with no DR matches, the presence of either a positive lymphocyte-growth assay or IgG anti-major-histocompatibility complex (MHC) class II antibodies was independently associated with high probability of progression to rejection (64% and 66%, respectively, p<0.0005). When both assays were positive, concomitantly with a low-grade endomyocardial biopsy, the positive predictive value for progression to a high-grade rejection was 86% (p<0.0001). For endomyocardial-biopsy grades 1B or 2, a positive lymphocyte-growth assay alone was associated with high-grade rejection in 100% of cases.


CONCLUSIONS
Use of an algorithm combining three immunological factors at the time of a low-grade endomyocardial biopsy enables prospective stratification of cardiac transplant recipients into risk categories for progression to high-grade rejection. Low-risk individuals require fewer biopsies, moderate-risk individuals require an ongoing schedule of surveillance biopsies, and high-risk individuals require rational organisation of interventional strategies aimed at preventing rejection. Additional predictive factors are needed to identify moderate-risk individuals who will progress to rejection. Ultimately, successful intervention may have an impact on the subsequent complication of TCAD.
Itescu
S
S
College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. si5@columbia.edu
Tung
T C
TC
Burke
E M
EM
Weinberg
A D
AD
Mancini
D
D
Michler
R E
RE
Suciu-Foca
N M
NM
Rose
E A
EA
D000328:Adult; D000465:Algorithms; D001706:Biopsy; D003327:Coronary Disease / Q000453:epidemiology* / Q000276:immunology; D004699:Endocardium / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology*; D006684:HLA-DR Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000706:statistics & numerical data; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D015993:Life Tables; D016015:Logistic Models; D008213:Lymphocyte Activation; D008297:Male; D009206:Myocardium / Q000473:pathology; D011183:Postoperative Complications / Q000453:epidemiology* / Q000276:immunology; D011237:Predictive Value of Tests; D018570:Risk Assessment; D013997:Time Factors
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II