Specificity of preformed alloantibodies causing B cell positive flow crossmatch in renal transplantation.
The specificity of alloantibodies (alloAb) and their clinical significance in association with T-/B+ flow cytometry crossmatch (FCXM) in kidney transplantation are not clearly defined. This study was undertaken to examine the HLA specificity and clinical relevance of Ab causing B+ FCXM in pre-transplant (final XM) recipients' serum samples. Final FCXM serum samples were analyzed from 457 renal transplant patients followed for 10 months post-transplantation. Two hundred and sixty patients had T-/B+ final FCXM. The control group included 197 recipients with T-/B- FCXM at time of transplantation. Class I/class II PRA and specificity of anti-HLA class I and class II Ab in final FCXM serum samples were analyzed by FlowPRA Class I Screening Test and FlowPRA Class II Screening Test. We found no correlation between graft outcome and pre-transplant T-/B- and T-/B+ FCXM status. Additionally, we observed no clinical relevance of B+ FCXM in retransplant patients. However, MCS > or =200 in B+ FCXM retransplant recipients was associated with anti-class II Ab to previous mismatches in regrafted patients (n = 46). This finding was confirmed by specificity analysis of anti-DR/DQ Ab in patients with high ( > or =15%) class II PRA. In 63% (12 of 19) of retransplants having T-/B+ FCXM, we defined the specificity of alloAb to first graft mismatched class II antigens. In contrast, anti-class II Ab was detected in only 5.7% (2 of 35) of single-graft recipients with different PRA values. Significantly greater MCS (240 +/- 61 vs. 163 +/- 48; p = 0.022) was observed in retransplant patients having short ( < or =5 m) previous graft survival time (PGST) than in those with long PGST ( > or =5 m). Only 2% of retransplant recipients with B + FCXM had non-HLA Ab. In contrast, the overwhelming majority of primary recipients had no detectable alloAbs. No significant difference in class I PRA was found between B- and B+ FCXM recipients. However, class II PRA was significantly higher in patients having B + FCXM (p = 0.028). Collectively, these data show that MCS intensity is not always a reliable criterion for anti-HLA Ab detection because of the presence of non-HLA Ab. These results can be explained by low titers of anti-class II Ab, at which concentration these Ab cannot produce a deleterious effect. FlowPRA and Flow screen beads appeared to be reliable and sensitive methods for detection and specificity analysis of anti-class II alloAb.
Lobashevsky
A L
AL
University of Alabama Hospital, Department of Surgery, Birmingham 35294, USA.
Senkbeil
R W
RW
Shoaf
J
J
Mink
C
C
Rowe
C
C
Lobashevsky
E S
ES
Burke
R
R
Hudson
S
S
Deierhoi
M H
MH
Thomas
J M
JM
D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007518:Isoantibodies