Background: ABMR episodes involve multiple immunologic and inflammatory pathways. IL-6/IL-6R interactions have pleiotropic effects on immunity and inflammation and may have relevance to ABMR. Recent studies have shown elevated sIL-6R and IL-6 in various inflammatory disorders, suggesting a pathogenic role. Here, we measure plasma sIL-6R and IL-6 levels pre- and post-Tx in HS pts who experienced ABMR, cellular-mediated rejection (CMR), acute tubular necrosis (ATN) or calcineurin inhibitor toxicity (CNI) to determine a possible role for IL-6/IL-6R in mediation.
Methods: Archived plasma obtained pre and post-Tx (at & prior to [14±11 days] biopsy) from 15 HS pts who had a biopsy (8 ABMR and 7 non-ABMR [3CMR, 2ATN, 2CNI]) were submitted for sIL-6R ELISA and IL-6 Luminex assays. 10 healthy individuals were also tested. The results were compared between ABMR vs. non-ABMR groups. The unit was ng/ml for sIL-6R and pg/ml for IL-6.
Results: Pre-Tx sIL-6R levels in HS pts were similar to those in normal individuals (123±42 vs. 115±44, NS). There was no significant difference in pre-Tx sIL-6R (108±40 vs. 144±42, p=0.1) and IL-6 levels (0.9±2.0 vs. 1.4±2.8, NS) between ABMR vs. non-ABMR groups. In the ABMR group, sIL-6R levels did not significantly change post-Tx (119±51, NS), but significantly increased when ABMR was diagnosed (166±53, p=0.049). In contrast, sIL-6R decreased slightly post-Tx (103±21, p=0.06) and significantly decreased further at CMR, ATN or CNI (84±14, p=0.006 vs. pre-Tx, p=0.003 vs. ABMR). All 8 pts (100%) in the ABMR and all 7 pts (100%) in the non-ABMR groups showed the elevated or decreased sIL-6R, respectively, compared to levels prior to the episode. IL-6 levels tended to be higher post-Tx compared to pre-Tx in the ABMR group (1.5±2.2, p=0.19) and further increased at ABMR episode (8.9±16.4, p=0.17), but this change was not statistically significant. IL-6 levels at CMR, ATN or CNI did not change compared to pre-Tx levels (1.8±3.3, NS).
Conclusion: Elevated plasma sIL-6R during ABMR episodes suggests a role for IL-6/IL-6R interactions and may be important as a diagnostic tool. In addition, targeting IL-6/IL-6R interactions may prove to be useful in treatment of ABMR.
To cite this abstract in AMA style:Shin B, Watanabe J, Ge S, Vo A, Jordan S, Toyoda M. Plasma Soluble IL-6 Receptor (SIL-6R) Levels Are Significantly Elevated during Antibody-Mediated Rejection (ABMR) in Highly-HLA Sensitized Renal Allograft Recipients (HS Pts) [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/plasma-soluble-il-6-receptor-sil-6r-levels-are-significantly-elevated-during-antibody-mediated-rejection-abmr-in-highly-hla-sensitized-renal-allograft-recipients-hs-pts/. Accessed June 14, 2021.
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