UNIVERSAL PROFILES OF REJECTION AND INFECTION IN ORGAN TRANSPLANTS.

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UNIVERSAL PROFILES OF REJECTION AND INFECTION IN ORGAN TRANSPLANTS.
Natalia Shulzhenko MD PhD ¹, Andrey Morgun MD PhD ¹, Ainhoa Perez-Diez PhD ³, Rosiane Diniz MD PhD ², Dirceu Almeida MD PhD ², Gerdine Sanson PhD ¹, Polly Matzinger PhD ³ and Maria Gerbase-DeLima MD PhD ¹. ¹ Immunogenetics, Univeresidade Federal de Sao Paulo, Sao Paulo, SP, Brazil ; ² Cardiology, Univeresidade Federal de Sao Paulo, Sao Paulo, SP, Brazil and ³ LCMI, NIH, Bethesda, MD, USA .

In the present study we compared gene expression between rejection, no rejection, and T. cruzi infection using microarrays with 14,000 genes, in 92 cardiac biopsies from 42 heart recipients. For analyses we used a training group of samples to build sets of gene predictors and two separate test groups to validate the results. We found a set of 98 genes (p<0.001) whose expression pattern is typical of acute rejection. It recognized not only all histologically diagnosed rejections but could also detect or predict some clinically important rejections that were missed by histology. The majority of samples with T. cruzi infections were classified by this pattern as rejections, revealing the similarity of immune profiles between rejection and infection. Further analysis showed that there is a distinct molecular signature of 87 genes (p<0.001) that discriminates infection from rejection. This signature was able to predict infection from biopsies that appeared quiescent, about 1-2 months before the disease could be histologically or clinically diagnosed. We also applied profiles discovered in hearts to previously published kidney data revealing correctness of 96% for diagnosis of kidney acute rejection and 89% for infections in kidneys. Although we based our predictors on heart transplants and Chagas infections, the resulting profiles were also able to accurately diagnose kidney rejections and their accompanying bacterial infections, suggesting that there are universal biological profiles that characterize rejections and infections in different types of transplants.