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.
College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. si5@columbia.edu
S
S
Itescu
T C
TC
Tung
E M
EM
Burke
A D
AD
Weinberg
D
D
Mancini
R E
RE
Michler
N M
NM
Suciu-Foca
E A
EA
Rose
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