Immunogenicity of Class I HLA but not preformed low MFI donor specific antibodies correlates with outcomes after first renal transplantation

A. Lobashevsky, W. Goggins, K. Rosner, Tim Taber

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs). Methods: All of the KTRs (n = 41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE. +, Group 2: DE-). Positivity for DE was determined based on the following criteria: biopsy proven transplant glomerulopathy (TG), de novo development of DSAs, increasing MFI values for preexisting DSAs, and the development of biopsy proven AMR. Anti-HLA antibodies were tested using single antigen Luminex technology. The HLAMatchmaker computer algorithm was used for the immunogenicity analysis of antibody verified (AbVer) mismatched eplets (MME) at the HLA-A and B loci. Results: The results of this study showed that the number of AbVer MME is larger (P = 0.03) in the group of KTR who developed DE. We also demonstrated that the number of AbVer MME is a strong predictor of post-transplant DE. These results indicate that persistent weakly reactive DSA is not a significant risk factor for the development of post-transplant DE and that recipients with such antibodies can be successfully transplanted. Conclusions: Immunogenicity of AbVer MME at HLA-A and B loci is strong predictor of post-transplant increases of the MFI values of preexisting or de novo developed DSA in the FC CM negative first KTR. Avoiding of transplants with more than eleven Class I AbVer MMEs may be the optimal approach to reduce the risk of kidney graft failure.

Original languageEnglish (US)
JournalTransplant Immunology
DOIs
StateAccepted/In press - Mar 7 2017

Fingerprint

Kidney Transplantation
Tissue Donors
Transplants
Antibodies
Kidney
Flow Cytometry
HLA-A Antigens
HLA-B Antigens
Immunoglobulin Isotypes
Biopsy
Renal Insufficiency
Anti-Idiotypic Antibodies
Cohort Studies
Technology
Antigens
Transplant Recipients

Keywords

  • Antibodies
  • Eplets
  • Immunogenicity
  • Kidney
  • MFI
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation

Cite this

@article{4239f553aa52489ebbb2e14e2ac92780,
title = "Immunogenicity of Class I HLA but not preformed low MFI donor specific antibodies correlates with outcomes after first renal transplantation",
abstract = "Background: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs). Methods: All of the KTRs (n = 41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE. +, Group 2: DE-). Positivity for DE was determined based on the following criteria: biopsy proven transplant glomerulopathy (TG), de novo development of DSAs, increasing MFI values for preexisting DSAs, and the development of biopsy proven AMR. Anti-HLA antibodies were tested using single antigen Luminex technology. The HLAMatchmaker computer algorithm was used for the immunogenicity analysis of antibody verified (AbVer) mismatched eplets (MME) at the HLA-A and B loci. Results: The results of this study showed that the number of AbVer MME is larger (P = 0.03) in the group of KTR who developed DE. We also demonstrated that the number of AbVer MME is a strong predictor of post-transplant DE. These results indicate that persistent weakly reactive DSA is not a significant risk factor for the development of post-transplant DE and that recipients with such antibodies can be successfully transplanted. Conclusions: Immunogenicity of AbVer MME at HLA-A and B loci is strong predictor of post-transplant increases of the MFI values of preexisting or de novo developed DSA in the FC CM negative first KTR. Avoiding of transplants with more than eleven Class I AbVer MMEs may be the optimal approach to reduce the risk of kidney graft failure.",
keywords = "Antibodies, Eplets, Immunogenicity, Kidney, MFI, Transplantation",
author = "A. Lobashevsky and W. Goggins and K. Rosner and Tim Taber",
year = "2017",
month = "3",
day = "7",
doi = "10.1016/j.trim.2017.06.001",
language = "English (US)",
journal = "Transplant Immunology",
issn = "0966-3274",
publisher = "Elsevier",

}

TY - JOUR

T1 - Immunogenicity of Class I HLA but not preformed low MFI donor specific antibodies correlates with outcomes after first renal transplantation

AU - Lobashevsky, A.

AU - Goggins, W.

AU - Rosner, K.

AU - Taber, Tim

PY - 2017/3/7

Y1 - 2017/3/7

N2 - Background: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs). Methods: All of the KTRs (n = 41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE. +, Group 2: DE-). Positivity for DE was determined based on the following criteria: biopsy proven transplant glomerulopathy (TG), de novo development of DSAs, increasing MFI values for preexisting DSAs, and the development of biopsy proven AMR. Anti-HLA antibodies were tested using single antigen Luminex technology. The HLAMatchmaker computer algorithm was used for the immunogenicity analysis of antibody verified (AbVer) mismatched eplets (MME) at the HLA-A and B loci. Results: The results of this study showed that the number of AbVer MME is larger (P = 0.03) in the group of KTR who developed DE. We also demonstrated that the number of AbVer MME is a strong predictor of post-transplant DE. These results indicate that persistent weakly reactive DSA is not a significant risk factor for the development of post-transplant DE and that recipients with such antibodies can be successfully transplanted. Conclusions: Immunogenicity of AbVer MME at HLA-A and B loci is strong predictor of post-transplant increases of the MFI values of preexisting or de novo developed DSA in the FC CM negative first KTR. Avoiding of transplants with more than eleven Class I AbVer MMEs may be the optimal approach to reduce the risk of kidney graft failure.

AB - Background: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs). Methods: All of the KTRs (n = 41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE. +, Group 2: DE-). Positivity for DE was determined based on the following criteria: biopsy proven transplant glomerulopathy (TG), de novo development of DSAs, increasing MFI values for preexisting DSAs, and the development of biopsy proven AMR. Anti-HLA antibodies were tested using single antigen Luminex technology. The HLAMatchmaker computer algorithm was used for the immunogenicity analysis of antibody verified (AbVer) mismatched eplets (MME) at the HLA-A and B loci. Results: The results of this study showed that the number of AbVer MME is larger (P = 0.03) in the group of KTR who developed DE. We also demonstrated that the number of AbVer MME is a strong predictor of post-transplant DE. These results indicate that persistent weakly reactive DSA is not a significant risk factor for the development of post-transplant DE and that recipients with such antibodies can be successfully transplanted. Conclusions: Immunogenicity of AbVer MME at HLA-A and B loci is strong predictor of post-transplant increases of the MFI values of preexisting or de novo developed DSA in the FC CM negative first KTR. Avoiding of transplants with more than eleven Class I AbVer MMEs may be the optimal approach to reduce the risk of kidney graft failure.

KW - Antibodies

KW - Eplets

KW - Immunogenicity

KW - Kidney

KW - MFI

KW - Transplantation

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U2 - 10.1016/j.trim.2017.06.001

DO - 10.1016/j.trim.2017.06.001

M3 - Article

C2 - 28629951

AN - SCOPUS:85021117353

JO - Transplant Immunology

JF - Transplant Immunology

SN - 0966-3274

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