Correlation Between Different Levels Of BK Virus Infection And Lymphocyte Subsets After Renal Transplantation

Background:Renal transplantation is the best treatment for end-stage renal disease(ESRD).The need for long-term immunosuppression in kidney transplant recipients reduces the incidence of rejection while also presenting an increased opportunity for infection.bk virus is universally susceptible in the population.After initial infection with BK virus,BK virus begins lifelong latency in renal tubular epithelial cells and urinary migratory epithelial cells.When immunity decreases it gradually progresses sequentially to BK viremia,BK viremia,and then gradually to BK virus-associated nephropathy,which poses a serious risk to the transplanted kidney.Due to the lack of specific anti-BK viral drugs,BK virus infection is gradually gaining attention from transplant management teams.Immunosuppressants mainly act on lymphocytes in the human immune system;therefore,studying the correlation between different levels of BK virus and lymphocyte subsets may serve as a breakthrough point for the clinical diagnosis and treatment of BK virus.Objective:To investigate the correlation between different levels of BK virus infection and lymphocyte subpopulations after renal transplantation and to investigate the predictive ability of lymphocyte subpopulations for different levels of BK virus infection.Methods:The follow-up data of 971 patients who underwent allogeneic kidney transplantation at the First Hospital of Jilin University from January 2018 to December 2021 were retrospectively analyzed until December 31,2022.A negative BK virus DNA load in urine and also negative blood was defined as the BK virus negative group,a BK virus DNA load>10~3 copies/m L in urine and a negative BK virus DNA load in blood was defined as the urinary BK virus positive group,and a BK virus DNA load>10~3copies/m L in blood and any value in urine was defined as the blood BK virus positive group.The results of urinary BK virus DNA load,blood BK virus DNA load,and lymphocyte subpopulations were collected from patients,along with information on age,sex,body mass index(Kg/m~2),length of time since transplantation(months),type of transplantation(DD or LD),and primary cause of kidney disease(nephritic disease,nephrotic disease,hypertensive nephropathy,diabetic nephropathy,and others).Comparisons between groups of lymphocyte subpopulations with different degrees of BK virus infection were performed using the Kruskal-Wallis nonparametric test,further rows with different overall distributions between groups were corrected for P-values using the Bonferroni method,and corrected P-values were used for correlation analysis using Spearman correlation,and lymphocyte subpopulation indicators with statistical significance were selected and ROC curves were plotted separately Their value for predicting BK virus infection(urinary BK virus positive or blood BK virus positive)and BK viraemia(blood BK virus positive)was analyzed.Result:(1)A total of 510 patients were enrolled in the study among 971 patients who were regularly followed up with both quantitative BK virus testing and lymphocyte subset testing.510 patients included 352 males(69%)and 158 females(31%),with a mean age of 42.03±11.83 years and a mean BMI of 22.97±2.86.A total of 510 patients were detected with urinary A total of 172 cases were detected positive for BK virus,with a urine positivity rate of 33.7%,and 46 cases were positive for blood BK virus,with a blood positivity rate of 9%.There were no significant differences between the three groups in terms of age,gender,body mass index,post-transplantation duration,type of transplantation,and primary cause of kidney disease.(2)The differences between the BK virus negative,urine BK virus positive and blood BK virus positive groups were statistically significant in terms of CD4~+T-cell percentage(36%,29%and 19%,respectively,P<0.001),CD4~+T-cell number(628,475 and 221,respectively,P<0.001),CD4/CD8(1.0,0.8 and 0.5,respectively,P<0.001)The differences between the BK virus-negative group and the blood BK virus-positive group were statistically significant in terms of CD3~+T-cell number(1309 and 824,,P=0.005),CD8~+T-cell ratio(33%and 42.5%,P=0.005),CD8~+T-cell number(618 and 532,P=0.041),The differences were statistically significant in terms of the number of NK cells(211 and 138.5,P=0.004).The differences between the BK virus negative group and the urinary BK virus positive group were statistically significant in terms of the proportion of CD8~+T-cell(33%and 37%,P=0.047).The differences between the severity of BK virus infection and the number of CD3~+T-cell,the proportion and number of CD4~+T-cell,the number of CD8~+T-cell,number of NK cells,and CD4/CD8were negatively correlated(r<0,P<0.05)and positively correlated with the proportion of CD8~+T-cell(r>0,P<0.05).(3)The best predictor of BK virus infection and BK viremia was CD4/CD8 with an area under the curve(AUC)of 0.668 and 0.789,followed by CD4~+T-cell ratio(0.647 and 0.761),CD4~+T-cell count(0.642 and 0.746),CD3~+T cell count(0.568 and 0.628),CD8~+T-cell ratio(0.584 and 0.620),NK cell count(0.580 and 0.605),and CD8~+T-cell count(0.545 and 0.603).The area under the curve of the combined predictors of lymphocyte subsets predicting BK virus infection and BK viremia was 0.742 and 0.849,respectively.Conclusion:(1)There was a correlation between different degrees of BK virus infection and lymphocyte subsets,with higher degrees of BK virus infection being associated with lower CD3~+T cell counts,CD4~+T cell ratios and counts,CD8~+T cell counts,NK cell counts,CD4/CD8,and higher CD8~+T cell ratios.(2)Lymphocyte subsets have good predictive value for BK virus infection and BK viremia after renal transplantation,with CD4/CD8 being the best predictor of BK virus infection and BK viremia.It is suggested that when lymphocyte subsets are reduced,especially CD4/CD8,timely antiviral therapy should be administered to prevent worsening of the infection if it is combined with BK virus infection,and when there is no evidence of BK virus infection,the possibility of recent BK virus infection should be alerted.