CHANGES IN SOLUBLE PD-L1 LEVELS IN SERUM AND PD-1/PD-L1 EXPRESSION IN KIDNEY TISSUE DURING ALLOGRAFT REJECTION AFTER KIDNEY TRANSPLANTATION

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Abstract Title *

CHANGES IN SOLUBLE PD-L1 LEVELS IN SERUM AND PD-1/PD-L1 EXPRESSION IN KIDNEY TISSUE DURING ALLOGRAFT REJECTION AFTER KIDNEY TRANSPLANTATION

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Co-author 1

Ayaka Hayashi a.hayashi.med@gmail.com The Jikei University School of Medicine Division of Nephrology and Hypertension, Department of Internal Medicine Tokyo Japan *

Co-author 2

Izumi Yamamoto izumi26@jikei.ac.jp The Jikei University School of Medicine Division of Nephrology and Hypertension, Department of Internal Medicine Tokyo Japan -

Co-author 3

Mayuko Kawabe mayuko1071@gmail.com The Jikei University School of Medicine Division of Nephrology and Hypertension, Department of Internal Medicine Tokyo Japan -

Co-author 4

Yutaro Ohki yutaro.19910625@gmail.com The Jikei University School of Medicine Division of Nephrology and Hypertension, Department of Internal Medicine Tokyo Japan -

Co-author 5

Takashi Yokoo tyokoo14@gmail.com The Jikei University School of Medicine Division of Nephrology and Hypertension, Department of Internal Medicine Tokyo Japan -

Co-author 6

Mitsuyoshi Urashima urashima.mitsu@gmail.com The Jikei University School of Medicine Division of Molecular Epidemiology Tokyo Japan -

Co-author 7

Co-author 8

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Co-author 10

Co-author 11

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Co-author 15

Introduction

Allograft rejection is one of the most significant factors in determining prognosis. Immune checkpoint molecules, such as programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1), interact with each other to suppress immune reactions. They are also important for establishing transplant immune tolerance. This exploratory study investigates changes in soluble PD-L1 levels and PD-1/PD-L1 expression in kidney allografts over time. The aim of the study is to compare PD-L1 behavior in rejection and non-rejection groups, and to investigate the potential of PD-L1 as a biomarker for kidney transplant rejection.

Methods

This study included 102 kidney transplant recipients at Jikei University Hospital in Tokyo, Japan. Soluble PD-L1 levels were measured at various time points from pre-transplantation to discharge, including cases of clinically or pathologically diagnosed with rejection, as well as non-rejection controls. Immunohistochemical staining of PD-1 and PD-L1 was also performed on kidney biopsy specimens, including zero-time kidney transplant biopsies, episode biopsies during admission, and post-discharge episode and protocol biopsies.

Results

Soluble PD-L1 levels remained stable post-transplantation but showed significant elevation during rejection episodes. Compared with the non-rejection group, soluble PD-L1 levels were significantly higher in the rejection group. Immunohistochemical analysis of kidney biopsy specimens from patients with rejection revealed increased PD-L1 expression.

Conclusion

Retrospective analysis of stored serum and kidney biopsy specimens revealed increased PD-L1 levels in serum and in kidney tissue during kidney transplant rejection. There may be an association between rejection and serum PD-L1 levels. These results suggest that serum levels of soluble PD-L1 have the potential to be used as a practical biomarker to detect kidney allograft rejection in early phase and could contribute to future clinical applications.

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