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.
|Inflammatory Proteins||p-value||Step-up p-value|
To cite this abstract in AMA style:Shaked A, Tobias J, Goodrich N, Gillespie B, Group theA2ALLStudy. Peripheral Expression of Inflammatory Proteins and miRNAs Expression at the Time of Biopsy Proven ACR and Persistence of Immune Activation Long after Clinical Resolution [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/peripheral-expression-of-inflammatory-proteins-and-mirnas-expression-at-the-time-of-biopsy-proven-acr-and-persistence-of-immune-activation-long-after-clinical-resolution/. Accessed October 26, 2020.
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