Clinical implications of flow cytometry crossmatch with T or B cells in living donor liver transplantation.
BACKGROUND
Acute allograft rejection (AR) in solid organ transplantation is generally regarded to develop through cell-mediated immune response following activation of helper T cells. Since production of antibodies is also mediated by helper T cells, humoral immunity may play some roles in AR. Although flow cytometry crossmatch (FCXM) is reported as a useful method for the detection of antibodies against donor antigen, specific role of T- or B-cell FCXM and its sensitivity for AR is controversial.


METHODS
T- and B-cell FCXM using fresh donor peripheral lymphocytes were performed before and after blood-type compatible living donor liver transplantation in 47 patients. IgM and IgG anti-donor antibodies were analyzed in relation to clinical AR.


RESULTS
Positive pre-transplant T-cell FCXM was associated with a high incidence of positive post-transplant T-cell FCXM (p=0.017). Four of five cases (80%) with positive pre-transplant T-cell FCXM experienced earlier AR (day 8.0+/-4.4, mean+/-SD) than 16 of 42 cases (31%) with negative pre-transplant T-cell FCXM (17.3+/-6.8; p=0.016). In addition, higher dose of steroids was given to treat AR episodes in cases with positive pre-transplant T-cell FCXM (79.9+/-10.3 mg/kg/month) than in those with negative pre-transplant T-cell FCXM (47.1+/-26.6; p=0.039). In the first month after transplantation, 13 episodes of positive post-transplant T-cell FCXM were all concomitant with or preceded clinical AR compared with seven ARs in T-cell FCXM-negative cases (p<0.0001). T-cell FCXM between positive sera and third parties revealed some crossreactions. In contrast, detection of antibodies by B-cell FCXM in pre- and post-transplant phases was scarcely associated with AR, and no correlation was found between T- and B-cell FCXM before and after transplantation.


CONCLUSIONS
Positive T-cell FCXM is closely related with AR and that before transplantation is a predictor of early and refractory AR as well as post-transplant FCXM. In contrast, not a few detections of antibodies irrelevant to AR are observed in B-cell FCXM, suggesting its low specificity.
Takakura
K
K
Department of Transplantation and Immunology, Kyoto University Faculty of Medicine, Kyoto, Japan. koji_takakura@po.fujisawa.co.jp
Kiuchi
T
T
Kasahara
M
M
Uryuhara
K
K
Uemoto
S
S
Inomata
Y
Y
Tanaka
K
K
D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007165:Immunosuppression Therapy; D007223:Infant; D016031:Liver Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*
D007074:Immunoglobulin G; D007075:Immunoglobulin M