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proteasome inhibition (1)

  • Mary Carmelle Philogene, Paul Sikorski, Robert A. Montgomery, Mary S. Leffell, and Andrea A. Zachary

    Background. Bortezomib has been used to reduce HLA antibody in patients either before transplantation or as treatment
    for antibody-mediated rejection (AMR). Reports on its efficacy show mixed results. The mechanism of action
    of this agent is via proteasome inhibition. The primary route of synthesis of HLA class I molecules is dependent on
    peptide generation by the proteasome, whereas that of class II is not. We observed a differential effect of bortezomib on
    class I versus class II antibody and hypothesized that this was related to a reduced expression of class I HLA antigens.
    Methods. The effect of bortezomib on HLA antibody levels was evaluated in 13 patients who were desensitized for
    incompatible renal…

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