Immunological monitoring of extracorporeal photopheresis after heart transplantation

Extracorporeal photopheresis (ECP) has been used as a prophylactic and therapeutic option to avoid and treat rejection after heart transplantation (HTx). Tolerance‐inducing effects of ECP such as up‐regulation of regulatory T cells (T_regs) are known, but specific effects of ECP on regulatory T cell (T_reg) subsets and dendritic cells (DCs) are lacking. We analysed different subsets of T_regs and DCs as well as the immune balance status during ECP treatment after HTx. Blood samples were collected from HTx patients treated with ECP for prophylaxis (n = 9) or from patients with histologically proven acute cellular rejection (ACR) of grade ≥ 1B (n = 9), as well as from control HTx patients without ECP (HTxC; n = 7). Subsets of T_regs and DCs as well as different cytokine levels were analysed. Almost 80% of the HTx patients showed an effect to ECP treatment with an increase of T_regs and plasmacytoid DCs (pDCs). The percentage of pDCs before ECP treatment was significantly higher in patients with no ECP effect (26·3% ± 5·6%) compared to patients who showed an effect to ECP (9·8% ± 10·2%; P = 0·011). Analysis of functional subsets of CD4⁺CD25^highCD127^low T_regs showed that CD62L‐, CD120b‐ and CD147‐positive T_regs did not differ between the groups. CD39‐positive T_regs increased during ECP treatment compared to HTxC. ECP‐treated patients showed higher levels for T helper type 1 (Th1), Th2 and Th17 cytokines. Cytokine levels were higher in HTx patients with rejection before ECP treatment compared to patients with prophylactic ECP treatment. We recommend a monitoring strategy that includes the quantification and analysis of T_regs, pDCs and the immune balance status before and up to 12 months after starting ECP.