The Correlation Analysis Among C4d Deposition, B And Plasma Cell Nodules Infiltration And Humoral Rejection Of Renal Allograft

Objective The refractory rejection is a major cause of impacting long-term allograft survival in kidney transplantation.It is usually insensitive or resistant to the prevalent therapeutic regimen,and usually causes allograft failure.Humoral-mediated rejection(HMR)is one type of refractory rejection,and HMR usually leads to allograft loss at last.Our study analyzed C4d deposition and the infiltration of B cells nodules and plasma cell nodules in renal allograft underwent refractory rejection;explored the relativities among B cells,plasma cells and humoral-mediated rejection(HMR),as well as the role of their positive expression in grafts loss.Methods This cohort study includes two groups.One group includes 40 excised kidney allograft samples with refractory rejection from June1989 to December 2006.The years of age:27-67,Male:28,Female:12.PRA＜10.%, CDC＜2%.The other group includes 20 biopsy samples from the kidney grafts that they were undergoing acute rejection episode.The allograft samples were embedded,deparaffined,stained with HE.C4d,CD20,CD38 and CD138 were detected by anti-C4d polyclonal antibody,anti-CD20 monoclonal antibody, anti-CD38 monoclonal antibody and anti-CD138 monoclonal antibody respectively through immunohistochemistry(IH).The relativities among the C4d, CD20,CD38 and CD138 were evaluated with Spearman rank correlation test,and their impacts on long-term graft survival had been studied by Log-Rank test and Kaplan-Meier survival curve.Results Among the 40 excised renal allograft specimens,17 cases showed C4d positive,19 showed CD20 positive,25 showed CD38 positive,23 showed CD38 positive,whose percentages were 42.5%,47.5%,62.5%and 57.5% respectively.Among the total,10 specimens were C4d single-positive(25.0%), 12 were CD20 single-positive(30.0%),7 were CD20 and C4d double-positive (17.5%).There were 5 cases for hyperacute rejection showed 2 cases for C4d positive(40%),1 case for CD20 positive(20%),1 case for CD38 positive(20%), 1 cases for CD138 positive(20%),23 cases for acute rejection showed 10 cases for C4d positive(43.4%),13 case for CD20 positive(56.5%),15 case for CD38 positive(60.9%),14 cases for CD138 positive(60.9%),12 cases for chronic rejection showed 5 cases for C4d positive(41.7%),5 case for CD20 positive (41.7%),9 case for CD38 positive(75%),8 cases for CD138 positive (66.7%),In the biopsy samples group,there were 2 cases showed C4d positive,2 cases showed CD20 positive,1 case showed CD38 positive,3 cases showed CD138 positive.A chi-square test showed that there were significant differences in acute rejections between two groups for the expression of C4d,CD20 and CD138 respectively(P＜0.05).The Spearman rank correlation test showed that C4d,CD38 and CD138 are all relative(P＜0.05),while there was no significant correlation between the presence of CD20-positive infiltration and C4d deposition in PTC(P＞0.05).Furthermore,Log-Rank test demonstrated that graft survival in recipients with both CD20 and C4d double-positive expression was significantly lower than that in recipients with C4d or CD20 single-positive expression(P＜0.05).Conclusion We found Humoral-mediated immunity and the infiltration of B-Cell Nodules and plasma cell Nodules all participated in the refractory rejection and they were all the high risk factors for long-term graft survival.Both CD20 and C4d double-positive expression in renal allografl were associated with poor graft survival.The expression of C4d,CD38 and CD138 were all relative,which suggested the plasma cell nodules infiltrated in renal allograft probably participated in the humoral rejection though secreting antibodies locally.There was no correlation between the presence of CD20-positive infiltration and peritubular C4d deposition in excised renal allograft.Therefore,the infiltration of CD20-positive B cells appeared not to participate in the mechanism of humoral rejection of renal allograft.