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An immunological algorithm to predict risk of high-grade rejection in cardiac transplant recipients
S Itescu1, T C Tung, E M Burke
1College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. si5@columbia.edu
Insights
Cardiac transplant recipients with frequent high-grade rejection are at higher risk for transplant-related coronary-artery disease. An algorithm combining biopsy, HLA-DR matching, and immunological assays can predict rejection progression.
Area of Science:
- Cardiology
- Immunology
- Transplantation Medicine
Background:
- Transplant-related coronary-artery disease (TCAD) is a frequent complication in cardiac allograft recipients, significantly limiting long-term survival.
- Understanding the predictors of TCAD is crucial for improving patient outcomes after heart transplantation.
Purpose of the Study:
- To examine the relationship between the cumulative frequency of high-grade rejection and the development of TCAD.
- To investigate if a combination of immunological factors can predict progression to high-grade rejection following a low-grade endomyocardial biopsy.
Main Methods:
- Kaplan-Meier actuarial life-tables were used to analyze TCAD and rejection frequency in 198 cardiac transplant recipients (1992-1996).
- Endomyocardial biopsy, lymphocyte-growth assays, and anti-HLA antibody measurements were assessed in 102 patients during the first post-transplant year.
- Predictive values for high-grade rejection were calculated using chi-squared tests, survival curves, and multivariable logistic regression.
Main Results:
- A direct correlation was found between cumulative annual rejection frequency and TCAD onset, with the highest risk observed at >0.75 rejections/year (p=0.0002).
- Donor-recipient HLA-DR matching, negative lymphocyte-growth assay, and absence of IgG anti-MHC class II antibodies were associated with protection against high-grade rejection.
- An algorithm combining these factors at low-grade biopsy accurately predicted progression to high-grade rejection (86% positive predictive value when both assays were positive).
Conclusions:
- An algorithm integrating three immunological factors with low-grade endomyocardial biopsy results allows for prospective risk stratification of cardiac transplant recipients.
- This stratification can guide surveillance strategies, reducing biopsies for low-risk patients and optimizing interventions for high-risk individuals.
- Further research is needed to identify additional predictors for moderate-risk patients, ultimately aiming to impact TCAD development.
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.
Findings:
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.
Interpretation:
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.