Long-Term Outcomes of Kidney Transplantation Across a Positive Complement-Dependent Cytotoxicity Crossmatch

Riella, Leonardo V.; Safa, Kassem; Yagan, Jude; Lee, Belinda; Azzi, Jamil; Najafian, Nader; Abdi, Reza; Milford, Edgar L.; Mah, Helen; Gabardi, Steven; Malek, Sayeed K.; Tullius, Stefan G.; Magee, Colm; Chandraker, Anil

doi:10.1097/01.tp.0000442782.98131.7c

Cited by 46 publications

(36 citation statements)

References 29 publications

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“…In addition, novel B-cell targeting agents, such as Rituximab or Bortezomib, and complement inhibitors have improved the management of theses patients [36][37][38]. Five-year patient and graft survival in a group of highly sensitized recipients of kidney transplants reached 86 and 72%, respectively, with the use of a combination of agents, such as TPE, IVIG and Rituximab [35].…”

Section: Key Pointsmentioning

confidence: 98%

“…Although the risk of AMR is significantly higher in sensitized patients, studies in kidney transplantation have demonstrated improved survival rates in those undergoing desensitization followed by transplantation when compared with those that continue waiting for an organ on the list [32]. A combination of total plasma exchange (TPE) and intravenous immunoglobulin (IVIG) is an effective desensitization regimen in SOT with good long-term outcomes in kidney transplantation [33][34][35]. In addition, novel B-cell targeting agents, such as Rituximab or Bortezomib, and complement inhibitors have improved the management of theses patients [36][37][38].…”

Section: Key Pointsmentioning

confidence: 99%

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Acute rejection in vascularized composite allotransplantation

Fischer

Lian

Kueckelhaus

et al. 2014

Current Opinion in Organ Transplantation

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Acute rejection is higher in VCA than in any other organ in the field of transplantation, although most episodes are controlled by high-dose steroids and optimization of maintenance immunosuppression. Because of limitations in patient number and the duration of follow-up, the long-term safety and effectiveness of VCA remain unclear. Moreover, the tests currently used to diagnose acute rejection are of limited value. Better diagnostic tools and a better understanding of the immunologic events during acute rejection are therefore needed to improve diagnosis, treatment and outcomes of this life-changing restorative surgery.

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Section: Key Pointsmentioning

confidence: 98%

Section: Key Pointsmentioning

confidence: 99%

Acute rejection in vascularized composite allotransplantation

Fischer

Lian

Kueckelhaus

et al. 2014

Current Opinion in Organ Transplantation

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“…Desensitization has increased transplant rates, reduced waiting times, and provided a significant survival benefit for patients with DSA compared with waiting for an HLA‐compatible transplant 8. Transplant of an HLA‐incompatible kidney after desensitization is, however, associated with an increased risk of ABMR, in both the short and longer term 4, 9…”

Section: Introductionmentioning

confidence: 99%

Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients

Lorant

Bengtsson

Eich

et al. 2018

American Journal of Transplantation

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Safety, immunogenicity, pharmacokinetics, and efficacy of the IgG‐degrading enzyme of Streptococcus pyogenes (IdeS [imlifidase]) were assessed in a single‐center, open‐label ascending‐dose study in highly sensitized patients with chronic kidney disease. Eight patients with cytotoxic PRAs (median cytotoxic PRAs of 64%) at enrollment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight ×2 [n = 3]; 0.25 mg/kg ×1 [n = 3], or 0.25 mg/kg ×2 [n = 2]). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days. Mean fluorescence intensity values of HLA class I and II reactivity were substantially reduced in all patients, and C1q binding to anti‐HLA was abolished. IdeS also cleaved the IgG‐type B cell receptor on CD19+ memory B cells. Anti‐IdeS antibodies developed 1 week after treatment, peaking at 2 weeks. A few hours after the second IdeS infusion, 1 patient received a deceased donor kidney offer. At enrollment, the patient had a positive serum crossmatch (HLA‐B7), detected by complement‐dependent cytotoxicity, flow cytometry, and multiplex bead assays. After IdeS infusion (0.12 mg/kg ×2) and when the HLA‐incompatible donor (HLA‐B7+) kidney was offered, the HLA antibody profile was negative. The kidney was transplanted successfully.

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“…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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Long-Term Outcomes of Kidney Transplantation Across a Positive Complement-Dependent Cytotoxicity Crossmatch

Abstract: Despite high rates of early rejection, desensitization in living-kidney transplantation results in acceptable 5-year patient and graft survival rates.

Cited by 46 publications

References 29 publications

Acute rejection in vascularized composite allotransplantation

Acute rejection in vascularized composite allotransplantation

Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients

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

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