The Impact of Proteasome Inhibition on Alloantibody-Producing Plasma Cells In Vivo

Diwan, Tayyab S.; Raghavaiah, Suresh; Burns, Justin M.; Kremers, Walter K.; Gloor, James M.; Stegall, Mark D.

doi:10.1097/tp.0b013e3182081333

Cited by 72 publications

(50 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…111 in an in vivo study of the effect of bortezomib on bone marrow plasma cells in highly allosensitized kidney transplant candidates, two of three patients treated with bortezomib had a significant decrease in CD138 + antibodysecreting cells following treatment. 112 although the investigations described above are pre liminary, they are indicators that interventions directed toward decreasing Dsa production may be feasible.…”

Section: Complement Blockadementioning

confidence: 97%

Sensitized renal transplant recipients: current protocols and future directions

Gloor

Stegall

2010

Nat Rev Nephrol

Self Cite

View full text Add to dashboard Cite

The identification of suitable donor kidneys for transplant candidates with high levels of circulating antibodies against human leukocyte antigen (HLA) is a major challenge and results in prolonged waiting times for transplantation. Technological advances in antibody characterization have permitted a more comprehensive assessment of anti-HLA antibody activity, as well as providing new insights into the clinical effect of HLA antibody class and specificity. Protocols have been developed that enable successful transplantation in patients with donor-specific antibodies (anti-HLA antibodies reactive against their donors). These protocols provide satisfactory early to intermediate-term allograft survival, and constitute an important advance in transplantation. Nevertheless, acute antibody-mediated rejection (AMR) remains a significant challenge, occurring in 20-50% of antibody-incompatible kidney transplantations. Although therapy directed toward lowering donor-specific antibody activity seems to be successful in reversing acute AMR, this condition still has an important negative impact on allograft survival. In addition, subclinical AMR seems to complicate a substantial proportion of positive-crossmatch transplantations even in the absence of allograft dysfunction, and may result in chronic histological abnormalities and shortened allograft function. New interventions for preventing acute AMR, such as anti-C5 antibody-mediated complement blockade and proteasome inhibitor-mediated plasma cell depletion, are promising therapeutic avenues currently under investigation.

show abstract

Section: Complement Blockadementioning

confidence: 97%

Sensitized renal transplant recipients: current protocols and future directions

Gloor

Stegall

2010

Nat Rev Nephrol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Bortezomib has been shown to decrease alloantibody production by bone marrowderived plasma cells and increase plasma cell apoptosis with a decrease in the amount of anti-HLA antibody detected [45 ,48]. It has also been shown to cause a significant decrease in CD138 þ antibody-secreting cells [49]. It was recently observed that naturally occurring CD4 þ CD25 þ regulatory T cells were noted to be resistant to its pro-apoptotic effect and that long-term culture of CD4 þ T cells in the presence of bortezomib promoted the emergence of a regulatory T-cell population that inhibited stimulated effector T cells [50], suggesting potential clinical benefit on 'pathologic' antibody production with decreased likelihood of impact on quiescent cells.…”

Section: Bortezomibmentioning

confidence: 98%

Immunosuppression in the sensitized heart transplant recipient

Eckman¹

2010

Current Opinion in Organ Transplantation

View full text Add to dashboard Cite

show abstract

“…Thus, rituximab per se does not lower anti-A/B blood group antibody titers [26] and therefore has always to be combined with an antibody removal procedure. Bortezomib -a proteasome inhibitor used for treatment of multiple myeloma -has recently been reported to directly target plasma cells [27]. Preliminary studies showed some effect for treatment of acute antibody-mediated rejection mediated by anti-HLA antibodies [28,29].…”

Section: Induction and Maintenance Immunosuppressionmentioning

confidence: 98%