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Novel Monitoring Panel for Tolerance-Inducing Effects of Extracorporal Photopheresis

M. Dieterlen, H. Bittner, S. Dhein, F. Mohr, M. Barten

Clinic for Cardiac Surgery, Heart Center Leipzig, Leipzig, Germany
Dept. Cardiothoracic Transplantation and Advanced Cardiac Surgery, Florida Hospital Orlando, Orlando

Meeting: 2013 American Transplant Congress

Abstract number: B1132

Goal: Extracorporal photopheresis (ECP) has been used as a therapeutic option for acute and chronic rejection after transplantation. Tolerance-inducing effects of ECP after transplantation are known like up-regulation of regulatory T cells (Tregs) in general, but specific ECP effects on Treg subsets and dendritic cells (DCs) are lacking. Thus, in our study, we monitored ECP effects on subsets of Tregs and DCs after heart transplantation (HTx).

Methods: Peripheral blood samples were collected from HTx recipients treated with ECP for the following reason (n=21 ECP treatments each group): (1) prophylaxis of acute cellular rejection (ACR) between month 3 to 6 post-HTx (n=8), or (2) histological proven ACR of grade ≥1B (ISHLT 1990, n=8). Each ECP treatment was performed at 2 subsequent days. Results of HTx recipients were compared to up-regulation of Tregs in peripheral blood of healthy human controls (HC; n=9). CD4+CD25highCD127low Tregs were further analysed for markers of activation (CD147) and of suppressing subsets (CD120b, CD62L, CD39) by FACS. DCs were analysed by FACS for myeloid (mDCs) and plasmacytoid (pDCs) subsets.

Results: The incidence of CD4+CD25highCD127low Tregs increased overall after ECP therapy with a pronounced effect in recipients with prophylactic ECP therapy (6.9%±0.7%) compared to the ECP-ACR group (6.0%±0.3%) and HCs (5.1%±0.7%). Treg activation marker CD147 was significantly up-regulated in the ECP prophylaxis group (99.7%±0.1%;p=0.026) compared to HCs (97.7%±0.8%). Whereas Treg markers of suppression CD120b and CD62L were significantly decreased in ECP-treated recipients compared to HCs but did not differ between the ECP groups. However, numbers of CD39+ Tregs, which are known to suppress pathogenic T helper17 cells, did not change after ECP therapy. In comparison to HCs, percentage of pDCs were reduced (14.5%±3.6% vs 26.0%±2.8%,p=0.016) and mDCs were increased (70.1%±4.0% vs 55.6%±3.7%,p=0.012) in prophylaxis group, but not in ECP-ACR group (pDCs:19.0%±4.7%,p=0.126; mDCs:66.2%±5.1%,p=0.069).

Conclusions: Our results showed that monitoring subsets of Tregs and DCs are valuable to monitor ECP therapy. Further studies on the mechanism of action of ECP effects on Tregs and DCs will help to identify responders and non-responders of ECP therapy afer transplantation.

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To cite this abstract in AMA style:

Dieterlen M, Bittner H, Dhein S, Mohr F, Barten M. Novel Monitoring Panel for Tolerance-Inducing Effects of Extracorporal Photopheresis [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/novel-monitoring-panel-for-tolerance-inducing-effects-of-extracorporal-photopheresis/. Accessed May 14, 2025.

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