Immunological monitoring of extracorporeal photopheresis after heart transplantation

Abstract

SummaryExtracorporeal 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 (Tregs) are known, but specific effects of ECP on regulatory T cell (Treg) subsets and dendritic cells (DCs) are lacking. We analysed different subsets of Tregs 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 Tregs 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 Tregs 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 high CD127 low Tregs showed that CD62L-, CD120b-and CD147-positive Tregs did not differ between the groups. CD39-positive Tregs 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 Tregs, pDCs and the immune balance status before and up to 12 months after starting ECP.

Indication‐specific immunomodulatory effects of extracorporeal photopheresis: A pilot study in heart transplanted patients

“…The increase of T regs is considered to be the initial mode of action of ECP, 13 and previous studies reported significantly increased T regs following ECP. 12,15,19 Thus, an increasing percentage of T regs has been defined as one criteria for a successful ECP treatment after HTx. 15 pDCs are known to support the expansion and induction of T regs and the maintenance of tolerance.…”

“…Peripheral blood samples obtained from the patients were treated and stained as described previously. 15,17 In brief, T regs were defined as CD3 + /CD4 + /CD25 high /CD127 low cells. Subsets of DCs were quantified by stainings using lineage cocktail-1, HLA-DR, CD11c, and CD123.…”

“…It is, therefore, of interest to answer these questions by gaining information about the ECP response on immune cells. Recently, results of a study showed that peripheral blood analysis of T regs and DC subsets as well as of the cytokine balance following ECP treatment could be helpful to define the duration and frequency of ECP therapy, as well as to treat patients more individually …”

“…Recently, results of a study showed that peripheral blood analysis of T regs and DC subsets as well as of the cytokine balance following ECP treatment could be helpful to define the duration and frequency of ECP therapy, as well as to treat patients more individually. 15 This led us to design a pilot study to investigate the immunological response to ECP in patients with acute ACR or CAV and in patients who received prophylactic ECP therapy.…”

The Value of Extracorporeal Photochemotherapy in Renal Transplant Rejection Inhibition

“…Методика применяется во всем мире в качестве терапии заболеваний, обусловлен-ных нарушением Т-клеточной системы иммуни-тета [2], и зарекомендовала себя как эффективный метод предупреждения и лечения отторжения при трансплантации сердца, легких и печени [3][4][5][6]. Из-вестны результаты нескольких исследований, где курсы ЭФХТ были с успехом использованы для ку-пирования устойчивых эпизодов отторжения почеч-ного аллотрансплантата (ПАТ) [7,8].…”