Acute humoral rejection of kidney allografts in patients with a positive flow cytometry crossmatch (FCXM)

Abstract

The patients with a positive flow cytometry crossmatch (FCXM) are categorized as a high-risk group causing hyperacute or accelerated acute rejection after kidney transplantation. According to the successful results of ABO-incompatible renal transplantation, we have performed the living related transplant operations in the recipients with positive FCXM for donor T cells, but having a negative complement-dependent lymphocytotoxic reaction test. We have followed the clinical course of 4 FCXM-positive patients, and 2 of them have developed acute humoral rejection. We report the strategies for FCXM-positive living kidney transplantations and the characteristics of pathological findings of acute humoral rejection in FCXM-positive renal transplants. We have had few episodes of acute humoral rejection in ABO-incompatible kidney transplantations under immunosuppressive regimens, including cyclophosphamide, but 2 patients of 4 with FCXM-positive kidney transplantations developed acute humoral rejections. The differences in immunosuppressive regimen between ABO-incompatible and FCXM-positive kidney transplantations concern anti-lymphocyte globulin (ALG) and splenectomy. We have not performed splenectomy and ALG administration in FCXM-positive kidney transplantations. Severe acute rejection episodes have been experienced on post-operative days 7 and 9 in 2 of 4 FCXM-positive recipients. The early acute rejection episodes were clinically and pathologically diagnosed as typical humoral rejections. We have examined an immunofluorescent study to prove the diagnosis of humoral rejection in FCXM-positive kidney transplantations; both immunoglobulin M and C3 were positive for the whole course of humoral rejection. The 2 patients with acute humoral rejection recovered after treatment with double filtration plasmapheresis or plasma exchange to remove their anti-donor antibodies. The gold standard of success in FCXM-positive kidney transplantations is to suppress the production and reduce the level of anti-donor antibodies after transplant operations.

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“…[3][4][5][6][7][8][9][10] However, in these reports the immunosuppressive agents and preoperative treatment are different from the present situation. Good outcomes using rituximab, plasma exchange (PEX), and intravenous immunoglobulin (IVIG) have been reported in immunologically high-risk patients.…”

“…Such patients often are positive for FCXM, which has higher sensitivity than complementdependent cytotoxicity. Many studies have reported a poor prognosis in FCXM T+B+ patients, [3][4][5][6][7][8][9][10] and transplant was considered contraindicated in these patients in some treatment centers, depriving these patients from receiving a transplant. In many of these reports, there was no discussion of desensitization, immunosuppressive agents used, or perioperative treatment, which may have differed from the present study.…”

C5 Blockade with Conventional Immunosuppression Induces Long-Term Graft Survival in Presensitized Recipients

“…Approximately 30% of kidney graft recipients become susceptible to AMR as a consequence of presensitization to donor antigens or sensitization following transplantation, particularly those who exhibit markedly elevated levels of circulating donor-reactive (HLA-specific) antibody (1,2). Current strategies are focused on reducing levels of pre-existing antibodies or attenuating primary humoral immune responses, including in vivo immunoadsorption, plasmapheresis and intravenous immunoglobulin, anti-CD20 treatment and splenectomy (5)(6)(7)(8)(9)(10)(11). Current strategies are focused on reducing levels of pre-existing antibodies or attenuating primary humoral immune responses, including in vivo immunoadsorption, plasmapheresis and intravenous immunoglobulin, anti-CD20 treatment and splenectomy (5)(6)(7)(8)(9)(10)(11).…”

Immunosuppression and Immune Monitoring After Renal Transplantation

“…This decline in the incidence of rejection is also notable for advances in the identification and treatment of “steroid‐resistant” rejection episodes, the majority of which are now known to be antibody mediated (4–7). These advances are not solely due to more effective immunosuppression medications, as advances in transplant crossmatching (8–13), identification of donor‐specific alloantibodies (14), and immunohistochemical identification of antibody‐mediated rejection by C4d staining (4,6,7,15–19) have all played a role. Still, it is not an exaggeration to say that acute cellular and antibody‐mediated rejection have become, for the majority of patients, treatable and reversible conditions.…”