Treatment of antibody‐mediated rejection in renal transplant patients: a clinical practice survey

Burton, Stephanie A.; Amir, Naaseha; Asbury, Alaina; Lange, A.R. De; Hardinger, Karen L.

doi:10.1111/ctr.12491

Cited by 53 publications

(37 citation statements)

References 37 publications

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“…Desensitization protocols with intravenous immunoglobulin (IVIG) in combination with plasmapheresis, rituximab, bortezomib, rabbit antithymocyte globulin and edulizumab are being used in sensitized recipients to reduce pre-transplant DSA and inhibit the increase in DSA post-transplantation (1, 2) (3). Despite these efforts, the rates of antibody-mediated rejection in sensitized patients remain significantly higher compared to non-sensitized recipients (4) (5), and there continues to be a need for better desensitization and immunosuppressive strategies.…”

Section: Introductionmentioning

confidence: 99%

Cutting Edge: CTLA-4Ig Inhibits Memory B Cell Responses and Promotes Allograft Survival in Sensitized Recipients

Chen

Wang

Yin

et al. 2015

The Journal of Immunology

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Sensitized recipients with pre-transplant donor-specific antibodies (DSA) are at higher risk for antibody-mediated rejection (AMR) than non-sensitized recipients, yet little is known about the properties of memory B cells that are central to the recall alloantibody responses. Using cell enrichment and MHC Class I tetramers, C57BL/6 mice sensitized with BALB/c splenocytes were shown to harbor H-2Kd-specific IgG+ memory B cells with a post-GC phenotype (CD73+CD273+CD38hiCD138−GL7−). These memory B cells adoptively transferred in naïve mice without memory T cells recapitulated class-switched recall alloantibody responses. During recall, memory H-2Kd-specific B cells preferentially differentiated into antibody-secreting cells (ASCs), whereas in primary response, H-2Kd-specific B cells differentiated into germinal center (GC) cells. Finally, our studies revealed that despite fundamental differences in alloreactive B cell fates in sensitized versus naive recipients, CTLA-4Ig was unexpectedly effective at constraining B cell responses and heart allograft rejection in sensitized recipients.

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Section: Introductionmentioning

confidence: 99%

Cutting Edge: CTLA-4Ig Inhibits Memory B Cell Responses and Promotes Allograft Survival in Sensitized Recipients

Chen

Wang

Yin

et al. 2015

The Journal of Immunology

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“…36,38 A recent clinical practice survey found that AMR treatments vary widely, with most centers using a combination of plasmapheresis and IVIg, with a number also incorporating rituximab. 39 Plasmapheresis and immunoadsorption directly remove IgG from the serum in a fairly predictable fashion but are inefficient inasmuch as IgG is removed only from the vascular space and then must reequilibrate with the interstitium before further antibody removal is optimal, a process that takes about 48 hours. There is evidence that low-dose IVIg dampens endogenous antibody rebound after depletion with plasmapheresis.…”

Section: Treatment Of Amrmentioning

confidence: 99%

Antibody-mediated rejection: New approaches in prevention and management

Montgomery

Loupy

Segev

2018

American Journal of Transplantation

116

102

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Estimated Time to Complete this Activity: 1.25 hours OverviewThis article reviews the pathophysiology of antibody-mediated rejection (AMR) with emphasis on the role of complement in allograft injury. It reviews the required features for a definitive diagnosis of AMR according to the latest Banff criteria, which incorporate recent findings delineating the complex spectrum of AMR and the diverse phenotypes seen. Clinical data on current and investigational treatments are summarized, and strategies to improve outcomes are presented. Lastly, a discussion of relevant predictive and surrogate endpoints provides a framework for future studies. Target AudienceThis activity has been designed to meet the educational needs of physicians, surgeons, scientists, nurses, organ procurement personnel, and pharmacists who care for patients with AMR. Educational ObjectivesAfter participating in this educational initiative, the participant should be better able to:• Explain the significance of activation of the complement system in the development of AMR Statement of SupportThis activity is jointly provided by RMEI Medical Education, LLC and Postgraduate Institute for Medicine. This activity is supported by an independent medical educational grant from Shire. For questions, please contact PIM at www.pimed.com. Joint Accreditation StatementIn support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and RMEI Medical Education, LLC. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Physician Continuing Medical EducationThe Postgraduate Institute for Medicine designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credit(s) TM . Physicians should claim only the credit commensurate with the extent of their participation in the activity. Continuing Pharmacy EducationPostgraduate Institute for Medicine is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.Postgraduate Institute for Medicine designates this continuing education activity for 1.25 contact hour(s) (0.125 CEUs) of the Accreditation Council for Pharmacy Education.[Correction added on 22 March, 2018, after first online publication: The accreditation statement and CEUs were updated.] (Universal Activity Number -0809-9999-17-584-H01-P) Please note: If you participated in the activity with UAN 0809-9999-16-209-L01-P, you are not able to claim credit for this activity.For Pharmacists: Upon successfully completing the post-test with a score of 75% or better and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service. Activity Type: Application Method of Participation and Request for CreditThere are no fees for participating and receiving CME credit for this...

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“…Currently, there are several therapies that may be used to prevent and treat AMR, including plasmapheresis, immunoadsorption, polyclonal antibodies, anti-CD20 monoclonal antibodies (Doxiadis and Claas, 2009;Iordan et al, 2009), immune globulin, rituximab, rabbit antithymocyte globulin (rATG), and eculizumab (Burton et al, 2015). However, since these methods do not eliminate or decrease the function of plasma cells, their therapeutic efficacy on AMR is often incomplete or short-lived (Perry et al, 2008(Perry et al, , 2009Stegall et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Bortezomib-based treatment of acute antibody-mediated rejection: a case report

Wang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Antibody-mediated rejection (AMR) is an important factor affecting survival after renal transplantation. A highly selective proteasome inhibitor, bortezomib, clears activated plasma cells from the body and has important therapeutic effect on AMR. We investigated the effects of bortezomib on AMR in a patient after a second renal transplant. Biopsy confirmed the diagnosis of mixed cellular rejection and AMR. Bortezomib was administered on day 1 (1.3 mg/m 2 ), day 4 (1.0 mg/m 2 ), and day 8 (1.0 mg/m 2 ). On the same days, 250 mg methylprednisolone was administered once, and cyclosporine dose (5 mg·kg -1 ·day -1 ) was reduced by 50%. Oral mycophenolate mofetil and steroid were withdrawn on day 1 of bortezomib treatment. Intermittent double-filtration plasmapheresis was also performed. We monitored parameters, including T lymphocyte subsets, CD139 and CD19 expression, panel reactive antibody (PRA), and serum creatinine concentration. At follow-up 6 months after bortezomib treatment, we observed: 1) serum creatinine stabilized at 130 μM from a peak level of 337 μM; 2) PRA decreased from a maximum of 66.7 to 0%; 3) blood plasma cell percentage rebounded after significantly decreasing following the first dose of bortezomib; 4) in renal allograft biopsy, immunohistochemical staining for C4d shifted from strongly positive to negative, and cellular rejection shifted from type IIA to borderline; and 5) adverse effects such as platelet suppression, hypotension, and grade 3 peripheral neuropathy emerged. Bortezomib effectively treated antibody-mediated renal transplantation rejection in this case study, but clinical trials with large sample sizes are still needed to explore clinical safety and tolerability.

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Treatment of antibody‐mediated rejection in renal transplant patients: a clinical practice survey

Abstract: Methods for the detection of AMR are similar, yet treatment of AMR varies widely. Most centers utilize DSA for detection and a combination of IVIG and plasmapheresis for treatment.

Cited by 53 publications

References 37 publications

Cutting Edge: CTLA-4Ig Inhibits Memory B Cell Responses and Promotes Allograft Survival in Sensitized Recipients

Cutting Edge: CTLA-4Ig Inhibits Memory B Cell Responses and Promotes Allograft Survival in Sensitized Recipients

Antibody-mediated rejection: New approaches in prevention and management

Bortezomib-based treatment of acute antibody-mediated rejection: a case report

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