Specificity of preformed alloantibodies causing B cell positive flow crossmatch in renal transplantation

• Published in: Clinical transplantation Vol. 14; no. 6; pp. 533 - 542
• Main Authors: Lobashevsky, Andrew L, Senkbeil, Rhonda W, Shoaf, James, Mink, Cindy, Rowe, Charyl, Lobashevsky, Elena S, Burke, Rebecca, Hudson, Sharon, Deierhoi, Mark H, Thomas, Judith M
• Format: Journal Article
• Language: English
• Published: Copenhagen Munksgaard International Publishers 01.12.2000; Blackwell
• Subjects: anti-HLA antibodies bead analysis; Antibody Specificity; B-Lymphocytes - immunology; Biological and medical sciences; Female; Flow Cytometry; Graft Rejection - immunology; Histocompatibility Antigens Class I - analysis; Histocompatibility Antigens Class II - analysis; Histocompatibility Testing; HLA Antigens - immunology; Humans; Immunosuppressive Agents - therapeutic use; Isoantibodies - immunology; kidney recipients; Kidney Transplantation - immunology; Male; Medical sciences; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; T cell negative/B cell positive flow cytometry crossmatch; T-Lymphocytes - immunology; Kidney disease; Human; Flow cytometry; HLA-System; Urinary system disease; Graft versus host reaction; Transplantation; Homotransplantation; Cross matching test; Kidney; Surgery; Alloantibody; Detection
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1034/j.1399-0012.2000.140604.x

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≥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 (≥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 (≤5 m) previous graft survival time (PGST) than in those with long PGST (≥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.