Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report

Tambur, Anat R.; Bestard, Oriol; Campbell, Patricia; Chong, Anita S.; Crespo, Marta; Ford, Mandy L.; Gebel, Howard M.; Heidt, Sebastiaan; Hickey, Michelle J.; Jackson, Annette; Kosmoliaptsis, Vasilis; Lefaucheur, Carmen; Louis, Kévin; Mannon, Roslyn B.; Mengel, Michael; Morris, Anna B.; Pinelli, David F.; Reed, Elaine F.; Schultz, Carrie S.; Taupin, Jean‐Luc; Valenzuela, Nicole M.; Wiebe, Chris; Nickerson, Peter

doi:10.1016/j.ajt.2022.11.009

Cited by 32 publications

(37 citation statements)

References 172 publications

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“…For example, our immunoassay may provide further insights into the clinical significance of HLA-specific antibodies detected in the context of transplantation. In this regard, the recently published recommendations of the Sensitization in Transplantation: Assessment of Risk (2022) Working Group highlighted the importance of measuring HLA-specific antibody strength (a combination of antibody concentration and affinity) to determine the efficacy of pre-transplant desensitisation and of antibody-mediated rejection treatment protocols, and to investigate the efficacy of different antibody-removal modalities (Tambur et al, 2023). The Group also emphasised the need for development of assays to measure HLA antibody affinity to better understand alloantibody pathogenicity and to determine the evolution of humoral anti-HLA alloimmune responses.…”

Section: Discussionmentioning

confidence: 99%

Microfluidic antibody affinity profiling of alloantibody-HLA interactions in human serum

Schneider

Scheidt

Priddey

et al. 2023

Biosensors and Bioelectronics

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Section: Discussionmentioning

confidence: 99%

Microfluidic antibody affinity profiling of alloantibody-HLA interactions in human serum

Schneider

Scheidt

Priddey

et al. 2023

Biosensors and Bioelectronics

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“…A DSA was deemed present if the mean fluorescence intensity (MFI) was $1400, with the caveat that when the antigen/allele in question belonged to a cross-reactive group (commonly referred to as CREG) or shared epitope(s), an MFI of .300 was considered positive. 34 Plasma Cytokines Plasma samples collected on days 7 and 30 after transplant obtained from the enrolled patients were assayed for inflammatory markers/cytokines IL-1b, IL-6, IL-8, and TNF using a MESO QuickPlex SQ120 using the V-PLEX Human Proinflammatory Panel II kit (Meso Scale Diagnostics, Rockville, MD) as per the manufacturer's instructions.…”

Section: Laboratory Studiesmentioning

confidence: 99%

Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial

Hricik

Alhamad

Brennan

et al. 2022

JASN

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Background: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates tumor necrosis factor alpha (TNF) production that amplifies allograft inflammation and may negatively impact transplant outcomes. Methods: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase II clinical trial. Two-hundred twenty-five primary transplant recipients of deceased-donor kidneys (KTx) (38.2% Black/African-American, 44% White) were randomized to receive i.v. infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated prior to \ kidney reperfusion. All subjects received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary endpoint was the difference between groups in mean 24-month estimated glomerular filtration rate (eGFR). Results: There was no difference in the primary endpoint, 24-mo eGFR between IFX (52.45 ml/min/1.73m2, 95% CI 48.38-56.52) vs. PLBO (57.35 ml/min/1.73m2, 95% CI 53.18-61.52, p=0.099). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ and day 7 post-KTx plasma analyses showed ~10-fold lower TNF (p<0.001) in IFX vs. PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) vs. PLBO (13.4% p=0.004) with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) vs. PLBO (4.9%, p=0.06). Conclusions: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peri-transplant inflammation as a strategy to improve KTx outcomes.

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“…The goal is to achieve a better understanding of their contribution to the transplant outcome. [46] • Although uncommon, it is possible that the patient may be reacting against a rare antigen that is not present in the SAB assay. [29] • High SAB cutoff: While the cutoff varies from center to center, most institutions that omit physical crossmatching consider an MFI between 1000 to 2000 as low immunological risk.…”

Section: Virtual Crossmatch: Better Than the Physical Crossmatch?mentioning

confidence: 99%

Crossmatch assays in transplantation: Physical or virtual?: A review

Rocha,

Jaramillo,

Neumann

et al. 2023

Medicine

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The value of the crossmatch test in assessing pretransplant immunological risk is vital for clinical decisions, ranging from the indication of the transplant to the guidance of induction protocols and treatment with immunosuppressants. The crossmatch tests in transplantation can be physical or virtual, each with its advantages and limitations. Currently, the virtual crossmatch stands out for its sensitivity and specificity compared to the physical tests. Additionally, the virtual crossmatch can be performed in less time, allowing for a reduction in cold ischemia time. It shows a good correlation with the results of physical tests and does not negatively impact graft survival. Proper communication between clinicians and the transplant immunology laboratory will lead to a deeper understanding of each patient’s immunological profile, better donor–recipient selection, and improved graft survival.

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Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report

Cited by 32 publications

References 172 publications

Microfluidic antibody affinity profiling of alloantibody-HLA interactions in human serum

Microfluidic antibody affinity profiling of alloantibody-HLA interactions in human serum

Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial

Crossmatch assays in transplantation: Physical or virtual?: A review

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