Annette M. Jackson, Edward S. Kraus, Babak J. Orandi, Dorry L. Segev, Robert A. Montgomery and Andrea A. Zachary
Rituximab has been used to increase the efficacy of desensitization protocols for human leukocyte antigen (HLA)-incompatible kidney transplantation; however, controlled comparisons have not been reported. Here we examined 256 post-transplant HLA antibody levels in 25 recipients desensitized with and 25 without rituximab induction, to determine the impact of B-cell depletion. We found significantly less HLA antibody rebound in the rituximab-treated patients (7% of donor-specific antibodies (DSAs) and 33% of non-DSAs) compared with a control cohort desensitized and transplanted without rituximab (32%
DSAs and 55% non-DSAs). The magnitude of the increase was significantly larger among patients who did not receive rituximab. Interestingly,…
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
Andrea A. Zachary , Renato M. Vega , Donna P. Lucas , and Mary S. Leffell
Solid phase immunoassays for the detection and characterization of HLA-speci fi c antibodies provide greatly increased sensitivity, speci fi city, and time and reagent ef fi ciency, compared to the traditionally used cell-based methods. Testing is performed using commercially available test kits. The assays are of two general types: enzyme-linked immunosorbent assays and multianalyte bead. The types vary in both sensitivity
and equipment requirements.
While these assays afford great improvement over the cell-based assays, they can be confounded by interference from substances within the serum that result in high background reactivity. The high sensitivity of the assays also makes them more susceptible to environmental factors and operator variability. The user must be…
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