The aim of this exploratory study was to determine whether inflammatory proteins and/or miRNA in serum specimens collected at the time of biopsy-proven rejection (ACR), and long after clinical resolution, can inform about pattern of peripheral immune activation during and after recovery from ACR.

Methods: A total of 124 serum samples from 44 recipients participating in the A2ALL study were available. Of these, 29 samples were taken at biopsy-proven ACR, and 77 at long term follow up. The pathology results of the biopsies were read at the A2ALL pathology core. Serum samples were analyzed using a 48-biomarker multi-analyte profile designed to discern protein inflammatory patterns, and miRNA array designed to identify 1718 human miRNA sequences. Pairs of conditions were specified for analysis. The p-values were calculated by t-test and corrected for multiple testing by Benjamini-Hochberg step up method.

Results: I. Non-HCV recipients: Up-regulated inflammatory protein profiles were present at the time of biopsy-proven ACR. When compared to non-rejectors, patients who experienced ACR remained with significantly persistent proinflammatory profiles long after rejection (table1). II. Non-HCV vs. HCV recipients: Inflammatory protein profiles at the time of biopsy proven ACR were similar during the rejection episode regardless of the HCV status except for elevated monocyte chemotactic protein 1 (p<0.04). In contrast, miRNA expression during rejection demonstrated different expression patterns in the two groups (table 2).

Conclusions: Individuals who experienced an episode of ACR continued to express activated inflammatory response long after clinical resolution suggesting persistent sub-clinical activation of alloimmune response. The long-term clinical significance of this phenomenon is not clear. The presence of HCV may alter rejection associated response pathways as evidenced by differential peripheral miRNA profiles.

« Back to 2013 American Transplant Congress