Partial Immunological Tolerance Induction with Extracorporeal Photopheresis

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Abstract

Purpose

to study both the mechanism of action of extracorporeal photopheresis (ECP) and its influence on frequency of rejection episodes and renal transplant function.

Materials and Methods

A prospective randomized study in 24 pairs of recipients has been conducted. One donor kidney was transplanted to a patient of the main group, the other – to the patient of the control group. The main group was treated with the following immunosuppressive therapy: Tac, MMF, prednisolone combined with 15 sessions of ECP; control group received immunosuppressive therapy only.

Materials and Methods

A percent (%) of naïve T-helpers expressing CD28 (CD3+CD4+CD27+CD28+CD45RO- phenotype) and mean fluorescence index (MFI) of the molecule were investigated. These parameters were assessed in healthy people, in the main and control groups on 4th and 30 th day after transplantation.

Results

In healthy people CD28 molecule is present on the whole surface of naïve T-helpers pool. However, its MFI is greatly variable.

Results

In recipients of renal transplant on 4th day after transplantation CD28+Th and MFI decrease significantly – p<0.001. MFI of CD28 molecules of naïve T-helpers decreases (p=0.005) proportionally to the number of these cells: r=0.58, p=0.01.

Results

In the main group on 30th day a significant decrease in percent of CD28+Th (p<0.001) and MFI (p<0.001) was observed in relation to the parameters on 4th day after transplantation. This dynamics in patients of the main group against the background of extracorporeal photopheresis can be indicative of a specific and universal inhibition of expression of co-activating molecules on naïve T-helpers.

Results

Patients in control group on 30th day after transplantation had no significant changes in percent of T-helpers expressing CD28, (p=0.42), and MFI (p=0.087).

Results

The number of CD28+Th in patients of the main group was statistically different from that of control group (p<0.001).

Results

Also in the main group the number of CD8 cells on 30th day was significantly lower than that on 4th day (p=0,02), as well as in control group (p<0.001).

Results

Clinical outcomes 1 month after transplantation patients of the main group had lower daily proteinuria values (p=0.01), after 180 days – lower daily proteinuria (p<0.001), serum creatinine (p=0.001) values and higher GFR (p<0.001) versus control group.

Results

In the main group during 6 months after transplantation there were no rejection episodes, in the control group there were 7 episodes (protocol biopsy after 1 and 6 months). Frequency of infectious complications in the main group was twice lower.

Conclusion

ECP is an effective method of transplant rejection prevention. This method helps to decrease the number of rejection episodes and improve transplant function. ECP is an inductor of partial immunological tolerance to transplant. The study assessing long-term outcomes is in progress.

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