Cross Reactive Epitope Group antibodies in sensitized kidneys transplant recipients was associated with early acute Antibody Mediated Rejection

Nainani, Neha; Singh, Neeraj; Shanahan, Thomas; Damodar, Amar; Parimoo, Nakul; Ummadi, Sudheer; Qazi, Yasir; Murray, Brian M.; Tornatore, Kathleen M.; Ciccirella, James C.; Blessios, George A.; Venuto, Rocco C.

doi:10.1016/j.trim.2008.10.009

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…The biopsy showed ABMR, described according to Banff criteria and without C4d deposits. Our results are similar to those described by Nainani et al [23], who showed that antibodies can react against the different CREG groups present in the donor, increasing the risk of early ABMR.…”

Section: Discussionsupporting

confidence: 92%

Clinical Case: Patient with Mixed Graft Rejection Four Days after Kidney Transplantation Developed Specific Antibodies against Donor Bw4 Specificities

Muñoz-Herrera¹,

Gutiérrez‐Bautista

López–Nevot

2021

Antibodies

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Kidney transplantation, like other transplants, has the risk of producing graft rejection due to genetic differences between donor and recipient. The three known types of renal rejection are listed in the Banff classification: T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), and mixed rejection. The human leukocyte antigens (HLA) are highly polymorphic and may be the targets of donor-specific antibodies, resulting in ABMR. Therefore, prior to transplantation, it is necessary to analyze the HLA genotype of the donor and recipient, as well as the presence of DSA, in order to avoid hyperacute rejection. However, due to the shortage of kidneys, it is very difficult to find a donor and a recipient with completely matched HLA genotypes. This can trigger a future rejection of the kidney, as is reported in this work. We describe a patient who received a kidney transplant after a negative DSA test, who developed graft rejection with antibodies against the donor’s HLA-Bw4 public epitope and lymphocytic infiltrate four days after transplantation, whose differential diagnosis was mixed rejection.

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Section: Discussionsupporting

confidence: 92%

Clinical Case: Patient with Mixed Graft Rejection Four Days after Kidney Transplantation Developed Specific Antibodies against Donor Bw4 Specificities

Muñoz-Herrera¹,

Gutiérrez‐Bautista

López–Nevot

2021

Antibodies

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“…These findings suggest that the use of non-DSA with the highest MFI as a predictor for pre-sensitizing HLA might be effective to some extent; however, we acknowledge that more cases are required for validation. Additionally, we analyzed the effect of shared BEs between the pre-sensitizing HLA and donor HLA on post-transplantation outcomes because the non-DSA toward BEs shared with the donor HLA were conventionally believed to be an immunological risk ( 15 ). In this study, 69 cases with non-DSA were analyzed and 47 cases were determined to share BEs between the pre-sensitizing HLA and donor HLA.…”

Section: Discussionmentioning

confidence: 99%

“…For example, organ allocation based on shared BEs, called CREG matching, was shown to reduce the frequency of sensitization to the donor HLA in a multicenter study ( 14 ). Furthermore, some recipients with preformed non-donor-specific anti-HLA antibodies (non-DSA) toward donor-CREG were reportedly associated with increased risks of early antibody-mediated rejection after transplantation ( 15 ). Recently, BEs in each HLA allele can be easily calculated using an in silico analytical tool known as the HLAMatchmaker.…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Shared T Cell Epitope Analysis in Early De Novo Donor-Specific Anti-HLA Antibody Production After Kidney Transplantation and Comparison With Shared B cell Epitope Analysis

et al. 2021

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In pre-sensitizing events, immunological memory is mainly created via indirect allorecognition where CD4+ T cells recognize foreign peptides in the context of self-HLA class II (pHLA) presented on antigen-presenting cells. This recognition makes it possible for naive CD4+ T-helper cells to differentiate into memory cells, resulting in the creation of further antibody memory. These responses contribute to effective secretion of donor-specific anti-HLA antibodies (DSA) after second encounters with the same peptide. Preformed donor-reactive CD4+ memory T cells may induce early immune responses after transplantation; however, the tools to evaluate them are limited. This study evaluated shared T cell epitopes (TEs) between the pre-sensitizing and donor HLA using an in silico assay, an alternative to estimate donor-reactive CD4+ memory T cells before transplantation. In 578 living donor kidney transplants without preformed DSA, 69 patients had anti-HLA antibodies before transplantation. Of them, 40 had shared TEs and were estimated to have donor-reactive CD4+ memory T cells. De novo DSA formation in the early phase was significantly higher in the shared TE-positive group than in the anti-HLA antibody- and shared TE-negative groups (p=0.001 and p=0.02, respectively). In conclusion, evaluation of shared TEs for estimating preformed donor-reactive CD4+ memory T cells may help predict the risk of early de novo DSA formation after kidney transplantation.

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“…The literature on the relevance of CREG in the field of LT is scarce. CREG positivity has been reported by Nainani et al as a risk factor for AMR in renal transplantation [ 30 ]. In their report, severe AMR developed in 4 out of 9 renal transplant recipients with preformed CREG antibodies and 2 patients achieved clinical remission with combined use of rituximab and IVIG.…”

Section: Discussionmentioning

confidence: 99%

Living Donor Liver Transplantation in Patients with Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibodies Using Preoperative Desensitization Therapy According to Intensity of Donor-Specific Antibodies: A Single-Center Study

Ogawa,

Tamura,

Sakamoto

et al. 2023

Ann Transplant

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Background In liver transplantation (LT), preoperative desensitization therapy is considered necessary in patients positive for donor-specific anti-human leukocyte antigen antibodies (DSAs). However, the relationship between DSA intensity and the necessary desensitization therapy is unclear. Material/Methods A total of 37 adult living donor (LD) LTs performed between January 2016 and March 2022 were examined. Mycophenolate mofetil (MMF) was administered preoperatively in DSA-positive cases with positive lymphocyte cross-matching who underwent LDLT. In those with strongly positive DSA (mean fluorescence intensity 10 000), rituximab was administered 2 weeks before LDLT in addition to MMF. Cross-reactive epitope group antigen (CREG)-alone-positive cases were also treated with preoperative MMF when lymphocyte cross-matching was positive. Results Of the 37 patients, 9 were DSA-positive, 7 were CREG-alone-positive, and the others were double-negative. Of 9 DSA-positive cases, desensitization therapy was performed in 7, among which rituximab administration was performed in 3 strongly DSA-positive cases. Of 7 CREG-alone-positive cases, 2 were lymphocyte cross-match-positive and underwent desensitization therapy. The 1-year survival rate was 100% in both DSA- and CREG-alone-positive cases. The frequency of T-cell mediated rejection in DSA-positive, CREG-alone-positive, and double-negative cases was 22%, 43%, and 29%, respectively, with no significant difference. Antibody-mediated rejection occurred in only 1 patient, who was strongly DSA-positive and blood-group incompatible. There was also no significant difference among the 3 groups in terms of the frequency of biliary complications or 90-day mortality. Conclusions Satisfactory LDLT results were achieved in DSA- and CREG-alone-positive cases following desensitization therapy.

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Cross Reactive Epitope Group antibodies in sensitized kidneys transplant recipients was associated with early acute Antibody Mediated Rejection

Cited by 7 publications

References 35 publications

Clinical Case: Patient with Mixed Graft Rejection Four Days after Kidney Transplantation Developed Specific Antibodies against Donor Bw4 Specificities

Clinical Case: Patient with Mixed Graft Rejection Four Days after Kidney Transplantation Developed Specific Antibodies against Donor Bw4 Specificities

Clinical Significance of Shared T Cell Epitope Analysis in Early De Novo Donor-Specific Anti-HLA Antibody Production After Kidney Transplantation and Comparison With Shared B cell Epitope Analysis

Living Donor Liver Transplantation in Patients with Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibodies Using Preoperative Desensitization Therapy According to Intensity of Donor-Specific Antibodies: A Single-Center Study

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