Impact of de novo donor‐specific HLA antibodies on pediatric kidney transplant prognosis in patients with acute declined or stable allograft function

In transplant recipients vaccination against Streptococcus pneumoniae is recommended to reduce mortality from invasive pneumococcal disease. It is still debated if vaccination in transplant recipients triggers alloresponses. Therefore, it was our aim to define if vaccination with Prevenar 13®, a 13-valent, conjugated pneumococcal vaccine (Pfizer, New York, NY, USA) that acts T cell dependently, induces human leukocyte antigen (HLA) antibodies in clinically stable kidney transplant recipients. Forty-seven patients were vaccinated once with Prevenar 13® and HLA antibodies were determined prior to vaccination and at month 1 and 12 thereafter. In parallel, pneumococcal IgG antibodies were measured. Using Luminex™ Mixed Beads technology (One Lambda/Thermo Fisher, Canoga Park, CA, USA) we observed overall no change in HLA antibodies after vaccination. Pneumococcal antibodies increased significantly at month 1 (p < 0.0001) and remained elevated at month 12 (p < 0.005). A more detailed analysis of HLA antibodies showed that in 18 females HLA class I and II antibodies increased significantly at month 1 and 12 (p < 0.05); whereas in 29 males HLA class I and II antibodies tended to decrease. Using Luminex™ Single Antigen Beads assay, no de novo donor-specific HLA antibodies were detected after vaccination. In conclusion, the current data indicate that females may be more susceptible to the induction of (non-specific) HLA antibodies after vaccination.

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An adjustable predictive score of graft survival in kidney transplant patients and the levels of risk linked to de novo donor-specific anti-HLA antibodies

PLoS ONE ◽

10.1371/journal.pone.0180236 ◽

2017 ◽

Vol 12 (7) ◽

pp. e0180236 ◽

Cited By ~ 5

Author(s):

Aurélie Prémaud ◽

Matthieu Filloux ◽

Philippe Gatault ◽

Antoine Thierry ◽

Matthias Büchler ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Survival ◽

De Novo ◽

Predictive Score ◽

Hla Antibodies ◽

Transplant Patients ◽

Kidney Transplant Patients

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Assessing the correlation between C3d-binding de novo donor specific HLA antibodies and rejection in kidney transplant recipients

Human Immunology ◽

10.1016/j.humimm.2015.07.197 ◽

2015 ◽

Vol 76 ◽

pp. 142

Author(s):

Matthew Cusick ◽

Kelley Haarberg ◽

John Friedewald ◽

Anat R. Tambur

Keyword(s):

Kidney Transplant ◽

De Novo ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Hla Antibodies

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Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection

Frontiers in Immunology ◽

10.3389/fimmu.2021.703457 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marta Crespo ◽

Laura Llinàs-Mallol ◽

Dolores Redondo-Pachón ◽

Carrie Butler ◽

Javier Gimeno ◽

...

Keyword(s):

Kidney Transplant ◽

De Novo ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Serum Samples ◽

Hla Antibodies ◽

Aortic Endothelial Cells ◽

Antibody Mediated Rejection ◽

Donor Specific Antibodies

BackgroundCorrelation between antibody-mediated rejection (ABMR) and circulating HLA donor-specific antibodies (HLA-DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of undetected HLA-DSA or non-HLA antibodies contributing to ABMR. Detailed evaluation of the degree of HLA matching together with the identification of non-HLA antibodies in KT may help to decipher the antibody involved.MethodsWe retrospectively assessed patients with transplant biopsies scored following Banff’15 classification. Pre- and post-transplant serum samples were checked for HLA and non-HLA antibodies [MICA-Ab, angiotensin-II type-1-receptor (AT1R)-Ab, endothelin-1 type-A-receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)]. We also analyzed HLA epitope mismatches (HLA-EM) between donors and recipients to explore their role in ABMR histology (ABMRh) with and without HLA-DSA.ResultsOne-hundred eighteen patients with normal histology (n = 19), ABMRh (n = 52) or IFTA (n = 47) were studied. ABMRh patients were HLA-DSApos (n = 38, 73%) or HLA-DSAneg (n = 14, 27%). Pre-transplant HLA-DSA and AT1R-Ab were more frequent in ABMRh compared with IFTA and normal histology cases (p = 0.006 and 0.003), without differences in other non-HLA antibodies. Only three ABMRhDSAneg cases showed non-HLA antibodies. ABMRhDSAneg and ABMRhDSApos cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMRhDSApos but not with ABMRhDSAneg. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 [1.31–10.37], p = 0.013) and AT1R-Ab (OR: 5.47 [1.78–16.76], p = 0.003) were independent predictors of ABMRhDSApos.ConclusionsIn conclusion, pre-transplant AT1R-Ab is frequently found in ABMRhDSApos patients. However, AT1R-Ab, MICA-Ab, ETAR-Ab or EC-XM+ are rarely found among ABMRhDSAneg patients. Pre-transplant AT1R-Ab may act synergistically with preformed or de novo HLA-DSA to produce ABMRhDSApos but not ABMRhDSAneg. HLA epitope mismatch associates with ABMRhDSApos compared with ABMRhDSAneg, suggesting factors other than HLA are responsible for the damage.

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