Proteasome Inhibitor-Based Primary Therapy for Antibody-Mediated Renal Allograft Rejection

Walsh, R. C.; Everly, J; Brailey, Paul; Rike, Adele; Arend, Lois J.; Mogilishetty, G.; Govil, Amit; Roy‐Chaudhury, Prabir; Alloway, Rita R.; Woodle, E. Steve

doi:10.1097/tp.0b013e3181c6ff8d

Cited by 181 publications

(177 citation statements)

References 19 publications

(27 reference statements)

Supporting

Mentioning

171

Contrasting

Unclassified

Order By: Relevance

“…In the context of AMR, PI seems to reduce the titers of immunodominant DSAs by 50%, especially in early AMR. 102 A similar but transient reduction rate has also been observed for preformed anti-HLA antibodies in a prospective trial of PI-based desensitization. 103 Interestingly, Woodle et al 103 also reported a low rate of dnDSA formation (12.5%) in patients who were desensitized.…”

Section: The Effect Of B or Plasma Cell-targeted Therapy On Dsasmentioning

confidence: 59%

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

Thaunat

Koenig

Leibler³

et al. 2016

JASN

View full text Add to dashboard Cite

The negative effect of donor-specific antibodies on the success of solid transplant is now clearly established. However, the lack of effective treatment to prevent the development of antibody-mediated lesions deepens the need for clinicians to focus on primary prevention of de novo humoral allosensitization. Among the factors associated with the risk of developing de novo donor-specific antibodies, therapeutic immunosuppression is the most obvious parameter in which improvement is possible. Beyond compliance and the overall depth of immunosuppression, it is likely that the nature of the drugs is also crucial. Here, we provide an overview of the molecular effect of the various immunosuppressive drugs on B cell biology. Clinical data related to the effect of these drugs on de novo humoral allosensitization are also examined, providing a platform from which clinicians can optimize immunosuppression for prevention of de novo donor-specific antibody generation at the individual level.

show abstract

Section: The Effect Of B or Plasma Cell-targeted Therapy On Dsasmentioning

confidence: 59%

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

Thaunat

Koenig

Leibler³

et al. 2016

JASN

View full text Add to dashboard Cite

show abstract

“…20 In addition, bortezomib has received recent attention in studies showing that it directly eliminates Ab-producing plasma cells and thus prevents Ab-mediated graft rejection after renal transplantation. [21][22][23] Moreover, improvement of platelet transfusion refractoriness was observed in a patient with HLA class I antibodies with the treatment of bortezomib for multiple myeloma. 24 The effectiveness of high-dose i.v.…”

Section: Discussionmentioning

confidence: 99%

Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT

Yoshihara

Maruya²,

Taniguchi

et al. 2011

Bone Marrow Transplant

196

201

View full text Add to dashboard Cite

A role of donor-specific HLA antibodies (DSA) in graft failure after SCT has been suggested, but the relevance of DSA in unmanipulated haploidentical SCT (haplo-SCT) remains unknown. We prospectively examined HLA antibodies using the Luminex-based single Ag assay for 79 adult patients undergoing unmanipulated haplo-SCT. Among them, 16 (20.2%) were HLA Ab-positive, including five patients with antibodies not corresponding to donor HLA Ags and 11 DSA-positive patients. Of the 11 DSA-positive patients, five received treatments to decrease DSA levels, including two, who received plasma exchange and rituximab, two who received platelet transfusions from healthy-related donors having DSAcorresponding HLA Ags and one who received bortezomib. Platelet transfusion was the most simple and effective treatment option for class I DSA. The cumulative incidence of neutrophil recovery was significantly lower in pretransplant (post-treatment) DSA-positive patients than in DSA-negative patients (61.9 vs 94.4%, P ¼ 0.026). Notably, three of five patients with high levels of DSA had graft failure. Donors should be selected on the basis of an evaluation of HLA antibodies. If haplo-SCT from donors with HLA Ags that correspond to high levels of DSA must be performed, then recipients should be treated for DSA to improve the chances of successful donor engraftment.

show abstract

“…This agent is now being used to attempt reduction of DSA in sensitized patients [92,93]. While many centers have incorporated this agent into treatment of AMR [94][95][96], its use for immunomodulation is limited to case reports. There have been 2 case reports that examined the use of bortezomib as a desensitizing agent pre-transplant.…”

Section: Future Of Crossmatch Incompatible Donorsmentioning

confidence: 99%

Transplanting Against Histocompatibility Barriers

Kannabhiran¹,

Lubetzky²,

Dadhania³

2012

Current Concepts in Kidney Transplantation

View full text Add to dashboard Cite

Proteasome Inhibitor-Based Primary Therapy for Antibody-Mediated Renal Allograft Rejection

Abstract: Proteasome inhibitor-based combination therapy provides a potential means for rapid DSA elimination in early acute AMR in renal transplant recipients.

Cited by 181 publications

References 19 publications

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT

Transplanting Against Histocompatibility Barriers

Contact Info

Product

Resources

About