FLOW CROSS-MATCHING IDENTIFIES PATIENTS AT RISK FOR POSTOPERATIVE ELABORATION OF CYTOTOXIC ANTIBODIES

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Abstract
Cytotoxic IgG against class I antigens can contribute to renal dysfunction or failure after transplantation. However, the clinical relevance of IgG measured by flow cytometric cross-matching is controversial. This study correlated pre- and postoperative flow reactivity with clinical outcome among renal transplant patients with negative preoperative cytotoxic cross-matches. Nonsensitized primary renal allograft patients (n=157) with negative preoperative cytotoxic cross-matches (complement-dependent lymphocytotoxicity assays) were stratified on the basis of IgG reactivity measured by flow cytometric cross-matching (FCXM) as FCXM negative (Neg) or positive against class I (T-pos FCXM) or class II (B-pos FCXM) antigens. The groups were compared in terms of frequency of early rejection and 1-year graft survival. Patient distribution was 67% Neg, 14% T-pos FCXM, 14% B-pos FCXM, and 5% IgM FCXM. The incidence of early rejection was 25±3% for Neg and 51±3% for T- and B-pos FCXM ( P <0.05). One-year graft survival for Neg versus T-pos and B-pos FCXM was 97±3% versus 44±10% ( P <0.05) and 77±5%( P =0.06), respectively. Rejections requiring plasmapheresis were found only among patients with T-pos FCXM. Among 29 patients, FCXM and complement-dependent lymphocytotoxicity assays were performed 10±2 and 28±4 days after transplantation. Pre- and posttransplant antibody levels were relatively unchanged among Neg and B-pos FCXM patient groups. In contrast, patients with T-pos FCXM produced cytotoxic IgG against class I after transplantation, which may have contributed to the severe graft dysfunction experienced by this group. FCXM is a useful tool to stratify primary renal transplant candidates in terms of potential risk for severe rejection. Furthermore, demonstration of preoperative flow reactivity against class I may identify a subgroup of patients at risk for early elaboration of cytotoxic alloantibody.