Minimal effect of bortezomib in reducing anti-pig antibodies in human leukocyte antigen-sensitized patients: a pilot study

作者：Hara Hidetaka; Bentall Andrew; Long Cassandra; Fang Jason; Andreyev Oleg; Lunz John; Ezzelarab Mohamed; Abu Elmagd Kareem M; Shapiro Ron; Ayares David; Stegall Mark; Cooper David K C^*

来源：Xenotransplantation, 2013, 20(6): 429-437.

DOI：10.1111/xen.12052

• antibodies
• anti-Gal
• antibodies
• anti-nonGal
• antibodies
• anti-pig
• bortezomib

BackgroundBortezomib, a proteasome inhibitor used to treat multiple myeloma, has been administered ( plasma exchange intravenous immunoglobulin [IVIg]) in attempts to reduce antibodies against human leukocyte antigens (HLA) in sensitized patients undergoing organ transplantation. To our knowledge, bortezomib has not been investigated for its effect on natural anti-pig antibodies. If bortezomib could reduce the production of anti-pig antibodies, this would likely be beneficial to the outcome of pig organ grafts in primates.
MethodsNine patients received bortezomib either to reduce anti-HLA antibody levels before organ allotransplantation or to treat antibody-mediated rejection. Patients at the Mayo Clinic (Group 1; n=4) received bortezomib alone, whereas at the UPMC (Group 2; n=5), this was combined with plasmaphereses +/- IVIg in some cases. Anti-pig IgM and IgG levels against wild-type (WT) and 1,3-galactosyltransferase gene knockout (GTKO) pig aortic endothelial cells (flow cytometryrelative mean fluorescence intensity) and anti-Gal IgM and IgG (ELISA-OD480nm) were measured pre- and post-bortezomib therapy.
ResultsMean anti-pig IgM levels were 11.2 (WT) and 1.9 (GTKO) pre-bortezomib treatment and 9.4 (WT: P=0.02) and 1.7 (GTKO: P=0.33) post-bortezomib treatment, respectively. Mean anti-pig IgG levels were 4.3 (WT) and 1.5 (GTKO) pre-bortezomib treatment and 3.6 (WT: P=0.21) and 1.4 (GTKO: P=0.20) post-bortezomib treatment, respectively. Mean anti-Gal IgM and IgG levels were 0.7 and 1.1, respectively, pre-treatment, and 0.6 (P=0.03) and 1.1 (NS), respectively, post-treatment. When the data were analyzed in Groups 1 and 2 separately, there were no significant differences between the pre- and post-bortezomib levels of anti-pig, anti-non-Gal, or anti-Gal IgM or IgG.
ConclusionsFrom this limited study, we conclude that bortezomib might reduce anti-Gal IgM levels in primates, but, in this respect alone, is unlikely to have any significant effect on the outcome of GTKO pig organ transplantation.

• 出版日期2013-11