| Objective Although with controversory from different research group,hepatitis B vaccination after liver transplantation,as an ideally alternative for replacement of LAM and/or HBlG,as well as has been investigated as another prophylatic strategy to HBV reinfection for achieving the goal of long term virus-free survival.How to reestablished a successful HBV active immunity involved many factors,and for which many reports mainly focused their attentions on clinical indications.Conversely, they put less concentrations on immunoenvironment,in fact,recovery of immune microenvironment is probably the first step in the development of antibody in recipients received HBV vaccine after liver transplantation. 1DO, as a suppressive immunomodulatory enzyme reported recently, and also as one of the factors impeded immunoreaction, could compromise immune response to vaccine.In this study,we investigated the characteristic of IDO metabolism path before and after vaccination from the standpoint of immunoenvironment,for the purpose of finding a solution to get better vaccination response. Methods 25 subjects received liver transplantation for HBV related liver end diseases,average time after LT was 33.32±14.81M(11-77M)when vaccination were administrated, all were given informed consent to program and the study was planed according to the guiding of local ethical committee.They were vaccinated with conventional double dose recombinant vaccine (Engerix-B) containing 40 ug HBsAg up to 4 times at monthes 0,1,2,6 (cyclel)under continuous LAM and/or HB1G prophylaxis.Another 25 healthy people as normal control were not given any interference.Fast blood were collected at pre-vaccination, 1W after 1th vaccination and 1W after 3th vaccination respectively. Concentrations of tryptophan and kynurenine were measured by HPLC in sera of subjects, and to estimate IDO activity, the kynurenine to tryptophan ratio was calculated. In parallel, HBV markers were measured by ELISA.PCR for HBV DNA and chemiluminescent microparticle Immunoassay for HBsAb quantification. Results 23 subjects had completed recorders at the end point.35%(8/23)had positive vaccination response,the average HBsAb titer increased form 75.675IU/L(28.370-147.600IU/L)at pre-vaccination to 184.224IU/L (59.190-668.500 IU/L) after finishing the schedule.IDO were slightly higher in all subjects pre-vaccination(mean,51.125 micromol/mmol in positive group and 54.040 micromol/mmol in negative group,respectively) compared to healthy individual(mean,48.493micromol/mrnol)(P>0.05). Inparallel, kynurenine(mean,3.394 micromol/L in positive group and 3.755 micromol/L in negative group,respectively) and tryptophan(mean,66.159 micromol/L in positive group and 72.265 micromol/L in negative group,respectively) were significant higher than normal control(2.664 micromol/L in kynurenine and 53.401 micromol/L in tryptophan,respectively).The statistic of Kyn in two groups compared to normal was P=0.003 and P=0.003,respectively; in parallel, the Trp in two sets was P=0.010 and P=0.001,respectively.However,no significant change could been seen in IDO. kynurenine and tryptophan in each group during the vaccination. Conclusion Positive response recipients who had a low or nearly normal level of IDO value and kynurenine concentration probably contributed to good response.IDO and its immunotoxic kynurenine suppressed immune response were one of the factors to poor vaccination. IDO and kynurenine decrease with tryptophan increase would imply the landmark of immuno-microenvironment recovery. |
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