Abstract 3337: The Role of IL1R2 and FLT3 Gene Expression in Cardiac Allograft Rejection: A Precise Measure of Corticosteroid Effect?
Background. Traditionally, corticosteroid efficacy in heart transplantation is measured by dose reduction while maintaining quiescence on biopsy. Recently, an 11 gene RT-PCR based panel has emerged as a marker of cardiac allograft rejection. This panel represents diverse genes including IL1R2 and FLT3 found to be corticosteroid responsive. We investigated the role of these 2 genes to anticipate future rejection and evaluated their modulation following rejection therapy.
Methods and Results. In a case-control design, 74 clinically quiescent heart transplant recipients (30–180 days post transplant) were enrolled. These included 28 who subsequently developed moderate-severe rejection (ISHLT grade 2R) within 12 weeks (rejection) and 46 who did not (controls). RNA was isolated at enrollment, during rejection and recovery (or matched times in controls). Both groups were on standard steroid weaning protocols, with no difference (p=0.75) in steroid dose for the index samples. IL1R2 was expressed 2.3-fold higher (p=0.0003) and FLT3 1.6 fold higher (p=0.02) in controls compared to rejectors during quiescence. On serial analysis, the expression of IL1R2 increased 2-fold from the index sample to the post-recovery sample for the rejection group and decreased in controls (p=0.0001). Expression of FLT3 followed a similar pattern (p=0.008).
[figure⇓] Conclusions. This investigation suggests that expression of IL1R2, a negative regulator of IL1 activity and FLT3, a receptor tyrosine kinase was a better measure of “steroid response” while steroid dose was not. Our findings point to the potential for using gene expression to guide immunosuppression in heart transplantation.