Potential benefit of mixed lymphocyte reaction assay-based immune monitoring after living donor liver transplantation for recipients with autoimmune hepatitis.
BACKGROUND
Recipients with autoimmune hepatitis (AIH) have a higher incidence of both rejection and recurrence after liver transplantation (LT) when compared with cholestatic liver diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). This is due to the lack of an immune monitoring system, making it difficult to control immunosuppressant agents. In this study, we examine the benefit of the carboxyfluorescein diacetate succinimidyl ester-mixed lymphocyte reaction (CFSE-MLR) monitoring system for evaluating the immune status in recipients with AIH and PBC/PCS after LT.


METHODS
Recipients who underwent LT (9 AIH and 11 PBC/PSC) from 2002 to 2013 at Hiroshima University were enrolled in this study. The correlation between the result of CFSE-MLR and the outcome, bacteremia, rejection, and/or recurrence was examined.


RESULTS
The cumulative survival rates for 5 years after LT revealed preferable outcomes for both groups (AIH 85.7%, PBC/PCS 80%). None of the recipients in the AIH group developed bacteremia during 90 days after LT, whereas three recipients from the PBC/PCS group (27%) developed bacteremia. The recurrence rate (AIH 33%, PBC/PSC 27%) was the same as the reported data; however, there was a lower incidence of acute rejection rate in our institution (AIH 11%, PBC/PSC 27%). In the CFSE-MLR assay, the stimulation index of CD4(+) T cells in the anti-self reaction was increased in recurrent cases, whereas no elevation of anti-donor reaction was observed in either CD4(+) or CD8(+) T cells.


CONCLUSIONS
Optimization of the immunosuppressant agents based on the CSFE-MLR assay after LT achieved a preferable outcome in recipients with both AIH and PBC/PCS. Therefore, CFSE-MLR assay might be a useful tool for predicting the recurrence of autoimmune liver diseases by monitoring anti-self reactivity of CD4(+) T cells.
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
H
H
Sakai
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: ishiyama@hiroshima-u.ac.jp.
K
K
Ishiyama
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
Y
Y
Tanaka
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
K
K
Ide
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
M
M
Ohira
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
H
H
Tahara
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
T
T
Abe
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
F
F
Hirata
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
H
H
Morimoto
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
S
S
Hashimoto
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
N
N
Tanimine
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
Y
Y
Saeki
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
S
S
Shimizu
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
T
T
Yano
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
T
T
Kobayashi
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
H
H
Tashiro
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
H
H
Ohdan
D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection; D019693:Hepatitis, Autoimmune / Q000276:immunology / Q000601:surgery*; D006801:Humans; D016031:Liver Transplantation; D019520:Living Donors; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D012008:Recurrence