Heightened expression of HLA-DQB1 and HLA-DQB2 in pre-implantation biopsies predicts poor late kidney graft function

Mine, Karina L.; Tedesco‐Silva, Hélio; Mourão, Tuíla B.; Campos, Érika F.; Salzedas, Larissa A.; Aguiar, Bruna L.; Felipe, Cláudia Rosso; Medina-Pestana, José; Gerbase‐DeLima, Maria

doi:10.1016/j.humimm.2018.05.002

Cited by 12 publications

(17 citation statements)

References 33 publications

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“…Out of the 143 cases included in the present study, 116 were from the previous study on HLA-DQB2 variant 2 expression in PIB (Mine et al, 2018).…”

Section: Study Populationmentioning

confidence: 99%

“…Our interest in HLA-DQB2 started with the unexpected finding, in a microarray study, of association between high HLA-DQB2 expression in preimplantation biopsies (PIB) of kidneys from young (18to 49-year olds) deceased donors (DD) and low graft function at 1 and 5 years posttransplantation (Mine et al, 2018). The HLA-DQB2…”

Section: Introductionmentioning

confidence: 99%

“…In the validation study concerning the association between high HLA-DQB2 expression in PIB and low graft function, performed in an independent cohort using reverse transcription-polymerase chain reaction (RT-PCR), HLA-DQB2 variant 2 expression behaved as an excellent predictor for low 1-year graft function, with expression levels ≥0.0025 relative units conferring an odds ratio of 22.5 and positive and negative predictive values of 71.4% and 90.0%, respectively (Mine et al, 2018). HLA-DQB2 variant 1 expression could not be analyzed in this validation study because, at that time, there was no commercially available assay for quantification of its expression.…”

Section: Introductionmentioning

confidence: 99%

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High soluble HLA‐DQB2 levels in posttransplant serum are associated with kidney graft dysfunction

Mine

Marco

Raimundo

et al. 2022

Int J Immunogenetics

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HLA-DQB2 is a gene of limited polymorphism, with unknown function that presents at least two transcript variants: v1, which encodes the full-length beta-chain, and v2, which lacks exon 4 and could give rise to a soluble protein. We previously showed a strong correlation between high v2 expression in preimplantation biopsies (PIB) of kidneys from young (18-to 49-year olds) but not from old, deceased donors and 1year posttransplant low (estimated glomerular filtration rate < 45 ml/min/1.73 m 2 ) graft function (GF). In this study, we aimed to investigate the impact of posttransplant soluble HLA-DQB2 (sDQB2) serum levels, v1 expression in PIB, and recipient HLA-DQB2 rs7453920 A/G polymorphism on GF. sDQB2 was evaluated by enzyme-linked immunosorbent assay in sera from 114 recipients, collected at least 1 year (median 2.1 years) after transplantation. Higher sDQB2 levels were observed in recipients of kidneys from young, but not from old, donors that had a ≥30% decline in GF within 1 year after blood collection for sDQB2 determination. Among the 15 recipients of kidneys from young donors with sDQB2 ≥ 1.52 ng/ml, 40% presented a ≥30% decline in GF, whereas this occurred in none of the 43 recipients with lower sDQB2 levels (p = 0.007; OR: 36.5). Expression of HLA-DQB2 variant 1, measured by reverse transcriptionpolymerase chain reaction (RT-PCR) in 92 PIB from young or old donors, did not significantly differ between transplants with high or low 4-year GF. HLA-DQB2 rs7453920 single nucleotide polymorphism (SNP) frequencies did not significantly differ between recipients with low or high 4-year GF. We conclude that HLA-DQB2 variant 1 expression in PIB and recipient rs7453920 SNP polymorphism are not associated with graft outcome. On the other hand, the association, in transplants of kidneys from young donors, between high posttransplant serum sDQB2 levels and decline in GF is a very interesting finding that deserves a validation study in a larger cohort.

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“…Out of the 143 cases included in the present study, 116 were from the previous study on HLA-DQB2 variant 2 expression in PIB (Mine et al, 2018).…”

Section: Study Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High soluble HLA‐DQB2 levels in posttransplant serum are associated with kidney graft dysfunction

Mine

Marco

Raimundo

et al. 2022

Int J Immunogenetics

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“…Neither of these factors are routinely taken into consideration when interpreting crossmatch assay results (Hönger et al, 2015). Variations in HLA expression may also lead to an unexpected crossmatch result, altering the interpretation of the clinical relevance of DSA identified by SPAs and potentially altering the associated risk of graft rejection in a donor-dependent manner (Carey et al, 2019;Mine et al, 2018;Thurman et al, 2019).…”

Section: Complement-dependent Cytotoxicity Crossmatching (Cdcxm)mentioning

confidence: 99%

Approaches for the characterization of clinically relevant pre‐transplant human leucocyte antigen (HLA) antibodies in solid organ transplant patients

Rosser

Sage

2021

Int J Immunogenetics

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The introduction of new immunosuppressive drugs in the 1980s able to minimize cellular rejection enabled successful solid organ transplantation and improved graft survival rates, even where Human Leucocyte Antigen (HLA) mismatched donor organs were transplanted (Muntean & Lucan, 2013;Thurman et al., 2019). While organ allocation schemes strive to minimize HLA mismatches, it is accepted that most transplants will have some level of HLA mismatch to ensure the effective utilization of a finite resource (Montgomery et al., 2018;NHS Blood & Transplant, 2019).Although HLA mismatches are permissible in solid organ transplantation, the presence of circulating antibodies directed against mismatched donor HLA antigens at the time of transplant can initiate acute antibody-mediated rejection (AMR), leading to graft dysfunction, endothelial inflammation and potential graft loss (Stites et al., 2015). These pre-transplant donor-specific HLA antibodies (DSA) can damage the organ through the activation of the complement cascade, through antibody-dependent cell-mediated cytotoxicity (ADCC) via Natural Killer (NK) cells and/or by direct opsonization

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“…However, it is also true that there is variation in the expression of class II antigens in pre-transplant tissues, which may depend on circulating cells. The initial expression of class II HLA antigens might determine transplantation outcomes [84]. On the other hand, following persistent tissue injury arising from rejection, infection, or drug toxicity the up-regulation of class II antigens might occur and they then become a target for class II DSA [85,86,87,88].…”

Section: Major Histocompatibility Complex In Organ Transplantationmentioning

confidence: 99%

The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage -

Nakamura

Shirouzu

Nakata

et al. 2019

IJMS

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Organ transplantation has progressed with the comprehension of the major histocompatibility complex (MHC). It is true that the outcome of organ transplantation largely relies on how well rejection is managed. It is no exaggeration to say that to be well acquainted with MHC is a shortcut to control rejection. In human beings, MHC is generally recognized as human leukocyte antigens (HLA). Under the current circumstances, the number of alleles is still increasing, but the function is not completely understood. Their roles in organ transplantation are of vital importance, because mismatches of HLA alleles possibly evoke both cellular and antibody-mediated rejection. Even though the control of cellular rejection has improved by recent advances of immunosuppressants, there is no doubt that antibody-mediated rejection (AMR), which is strongly correlated with donor-specific anti-HLA antibodies (DSA), brings a poor outcome. Thus, to diagnose and treat AMR correctly is a clear proposition. In this review, we would like to focus on the detection of intra-graft DSA as a recent trend. Overall, here we will review the current knowledge regarding MHC, especially with intra-graft DSA, and future perspectives: HLA epitope matching; eplet risk stratification; predicted indirectly recognizable HLA epitopes etc. in the context of organ transplantation.

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Heightened expression of HLA-DQB1 and HLA-DQB2 in pre-implantation biopsies predicts poor late kidney graft function

Cited by 12 publications

References 33 publications

High soluble HLA‐DQB2 levels in posttransplant serum are associated with kidney graft dysfunction

High soluble HLA‐DQB2 levels in posttransplant serum are associated with kidney graft dysfunction

Approaches for the characterization of clinically relevant pre‐transplant human leucocyte antigen (HLA) antibodies in solid organ transplant patients

The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage -

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