Use of Intravenous Immune Globulin and Rituximab for Desensitization of Highly Human Leukocyte Antigen-Sensitized Patients Awaiting Kidney Transplantation

Abstract

The article by Vo et al. (1) about transplanting highly sensitized patients is one of their most recent contributions in trying to tackle this recalcitrant problem. The authors used a rituximab and intravenous immune globulin desensitization protocol, which is simple to administer. This, however, together with the fact that the Cedars-Sinai group is well respected and that the protocol is proposed for highly human leukocyte antigen-sensitized patients (as shown in the title) is promoting its use worldwide with no results to justify the expense. Their definition of “highly sensitized” patients by flow panel reactive antibody is questionable. This test is sensitive but can give high percentage values with low or no sensitization (in contrast to the traditional cytotoxicity panel reactive antibody where high values usually go together with high titers). In addition, they do acknowledge that a number of their transplanted patients had flow crossmatches of less than 250 mean channel shifts, which they defined as “acceptable positive.” Many centers transplant these patients with increased immunosuppression but no desensitization. The authors mention that in some cases, patients received the treatment but the donor-specific crossmatch with the pretransplant specimen turned out to be low by chance. True, but this is certainly not a case of success because of the protocol. The authors also state that they would not transplant such patients without using their protocol, but they have not shown that patients with a weakly positive flow crossmatch do better with the protocol than without. Thus, it is not clear from the data how many patients would have had acceptable positive crossmatches before desensitization, or how many patients were treated and not transplanted. In addition, the effect of rituximab itself on alloantibody, and its indications in transplant patients, has not been established, as one of the authors acknowledged recently (2). Although a strict quantitative evaluation on the effect of rituximab plus intravenous immune globulin on human leukocyte antigen antibody levels remains to be done, the patients transplanted were obviously not highly sensitized against their donors. Indeed, at the end of the discussion, the authors themselves state that patients with lower donor-specific antibody levels benefit more and that no protocol deals well with highly sensitized patients. Some readers may miss this statement, but no one will miss the title. In summary, it has to be made clear that this protocol does not represent a solution for highly sensitized patients. Shehzad Rehman1 Herwig-Ulf Meier-Kriesche1 Juan Scornik2 1 Department of Medicine University of Florida Gainesville, FL 2 Department of Pathology University of Florida Gainesville, FL