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HEART ALLOGRAFT OUTCOME IS INDEPENDENTLY ASSOCIATED WITH RECIPIENTS’ GENETIC MAKEUP.
Nancy Herrera, Maria Rosa Costanzo and Anat R. Tambur. Chicago IL, USA, Rush U Med Ctr, 60612, HLA lab.

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Cytokines and growth factors play a key role in regulating cellular and humoral immune responses. Analysis of their impact on transplant outcome in heart allograft recipients, by using multivariate analysis, is presented.
The genetic profile of five cytokines [TNF-alpha G/A (–308); TGF-beta T/ C (+10), G/C (+25); IFN-gamma T/A (+874); IL-6 G/C (-174); IL-10 G/A (-1082), C/T (-819) A/C (-592)] and two growth factors [PDGF A/G (+286) A/C (+1135) VEGF A/G (+1154) A/C (+2578)] were studied in 72 heart allograft recipient, transplanted at Rush U. Med Ctr between 10/ 94 and 01/2001. Mean follow-up time was 28 months; age 47 yrs, 86% male, 35% AA. Allograft biopsies were scored using ISHLT criteria. Angiograms and Intra Vascular UltraSound (IVUS) studies were performed annually. Cellular and humoral rejection burden were calculated as the sum of grades divided by the number of events studied, divided by the follow-up time.
Among the growth factors, only the polymorphism at position 286 of PDGF showed correlation with transplant outcome. Patients with the AA phenotype had significantly higher likelihood of developing abnormal angiogram at 3 years post transplant (p<0.002). Patients with the AG phenotype had a lower cellular rejection burden (p<0.006). Abnormal angiograms were associated also with higher levels of IFN-gamma (p<0.02). Interestingly, more AA belonged to the low producer group of IFN-gamma, compared with Caucasians (p<0.0001). Lastly, increased Stanford score on IVUS – severe allograft vasculopathy – was highly correlated with low producer phenotype of both TGF-beta and IL-10 (p=0.002).
The genetic make up of heart transplant recipients, with regard to their cytokine and growth factor production levels, should be factored in when tailoring immunosuppression protocols.