Endomyocardial biopsies with different acute rejection gradings

Our goals were to determine whether (i) gene expression patterns in biopsies grouped by acute rejection grade (AR) would be consistent; (ii) a characteristic gene expression profile would be associated with ISHLT Grade 0, 1A & 1B (equivalent to 1R on recently revised criteria) and ISHLT grade 3A & 3B (equivalent to 2R & 3R on recently revised criteria); (iii) gene expression patterns emerging from the analysis would provide insights into mechanisms of AR. The samples used for gene expression profiling were endomyocardial biopsies (EMB) with different acute rejection gradings. The EMB (n=2726) were obtained from the right site of the interventricular septum of heart transplant recipients (n=2423) and graded according to the guidelines of the International Society for Heart and Lung Transplantation (ISHLT, grade 0, n=9; grade1A, n=5; 1B, n=5; 3A, n=4; 3B, n=43). Selection criteria for inclusion of patients in this analysis required the availability of appropriately stored EMB samples for RNA extraction; absence of any infection that required treatment with an antimicrobial drug at anytime during the posttransplant course of the patient; absence of prior AR rejection of any grade; absence of hemodynamic compromise at the time of EMB; use of standard immunosuppressive regimen; and the absence of HLA antibodies prior to transplant. An all pairs experiment design type is where all labeled extracts are compared to every other labeled extract.