Antibody-mediated rejection: prevention, monitoring and treatment dilemmas

Rodríguez-Ramírez, Sonia; Jurdi, Ayman Al; Konvalinka, Ana; Riella, Leonardo V.

doi:10.1097/mot.0000000000001011

Cited by 18 publications

(18 citation statements)

References 104 publications

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“…SAB assays will not be able to detect allele‐specific DSAs if their corresponding HLA alleles are unrepresented. Cases with AMR or positive cell‐based crossmatches but negative DSAs on SAB assays may also be explained by undetectable DSAs from unrepresented HLA alleles (Nishikawa et al., 2023; Rodriguez‐Ramirez et al., 2022; Schlaf et al., 2021; Thammanichanond et al., 2022).…”

Section: Discussionmentioning

confidence: 99%

“…In patients who develop AMR, the detection of DSAs using SABs not only constitutes an important aspect in the diagnosis but is also used to monitor treatment response (Loupy et al, 2020;Rodriguez-Ramirez et al, 2022;Schinstock et al, 2020). Therefore, the accuracy of SAB assays is paramount for the safe delivery of solid organ transplantation services.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of pre‐formed or de novo DSAs are associated with poorer prognosis and antibody‐mediated rejection (AMR) (Bachelet et al., 2016; Crespo et al., 2020; Schinstock et al., 2020; Willicombe et al., 2012; Ziemann et al., 2019). In patients who develop AMR, the detection of DSAs using SABs not only constitutes an important aspect in the diagnosis but is also used to monitor treatment response (Loupy et al., 2020; Rodriguez‐Ramirez et al., 2022; Schinstock et al., 2020). Therefore, the accuracy of SAB assays is paramount for the safe delivery of solid organ transplantation services.…”

Section: Introductionmentioning

confidence: 99%

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Unrepresented human leucocyte antigen alleles in single‐antigen bead assays: A single‐centre cohort study

Ho,

Phang,

Liew

et al. 2023

Int J Immunogenetics

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Human leucocyte antigen (HLA) alleles may generate antibodies that are undetectable by routine single‐antigen beads (SABs) assays if their unique epitopes are unrepresented. We aimed to describe the prevalence and explore the potential impact of unrepresented HLA alleles in standard SAB kits in our cohort. All individuals who had undergone two‐field HLA typing (HLA‐A/B/C/DRB1/DQA1/‐DQB1/‐DPA1/‐DPB1) from February 2021 to July 2023 were included. Two‐field HLA‐DRB3/4/5 typing was imputed. Each unrepresented allele was compared with the most similar represented allele in the standard LABScreen, LABScreen ExPlex (One Lambda) and the LIFECODES (Immucor) SAB kits. Differences in eplet expression (HLA Eplet Registry) were identified. Differences in three‐dimensional molecular structures were visualized using generated models (SWISS‐MODEL). Two‐field HLA typing was performed for 116 individuals. Overall, 16.7% of all HLA alleles, found in 36.2% of individuals, were unrepresented by all SAB test kits. Four eplets, found in 12.9% of individuals, were unrepresented in at least 1 SAB kit. Non‐Chinese individuals were more likely to have unrepresented HLA alleles and eplets than Chinese individuals. There were differences in HLA allele and eplet representation amongst the different SAB test kits. Use of supplementary SAB test kits may improve HLA allele and eplet representation. Although some HLA alleles were unrepresented, most epitopes were represented in current SAB kits. However, some unrepresented alleles may contain epitopes which may generate undetectable antibodies. Further studies may be needed to investigate the potential clinical impact of these unrepresented alleles and eplets, especially in certain ethnic populations or at‐risk individuals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Unrepresented human leucocyte antigen alleles in single‐antigen bead assays: A single‐centre cohort study

Ho,

Phang,

Liew

et al. 2023

Int J Immunogenetics

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“…4 All three types of AR have been associated with graft dysfunction and suboptimal graft and patient survival rates. 5–9…”

Section: Introductionmentioning

confidence: 99%

Urinary Cell Gene Signature of Acute Rejection in Kidney Allografts

Salinas,

Li,

Snopkowski

et al. 2023

Preprint

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IntroductionA kidney allograft biopsy may display acute T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), or concurrent TCMR + ABMR (MR). Development of noninvasive biomarkers diagnostic of all three types of acute rejection is a useful addition to the diagnostic armamentarium.MethodsWe developed customized RT-qPCR assays and measured urinary cell mRNA copy number in 145 biopsy-matched urine samples from 126 kidney allograft recipients and calculated urinary cell three-gene signature score from log10-transformed values for the 18S-normalized CD3E mRNA, 18S-normalized CXCL10 mRNA and 18S rRNA. We determined whether the signature score in biopsy-matched urine specimens discriminates biopsies without rejection (NR, n=50) from biopsies displaying TCMR (n=47), ABMR (n=28) or MR (n=20).ResultsUrinary cell three-gene signature discriminated TCMR, ABMR or MR biopsies from NR biopsies (P <0.0001, One-way ANOVA). Dunnett’s multiple comparisons test yielded P<0.0001 for NR vs. TCMR; P <0.001 for NR vs. ABMR; and P <0.0001 for NR vs. MR. By bootstrap resampling, optimism-corrected area under the receiver operating characteristic curve (AUC) was 0.749 (bias-corrected 95% confidence interval [CI], 0.638 to 0.840) for NR vs. TCMR (P<0.0001); 0.780 (95% CI, 0.656 to 0.878) for NR vs. ABMR (P<0.0001); and 0.857 (95% CI, 0.727 to 0.947) for NR vs. MR (P<0.0001). All three rejection biopsy categories were distinguished from NR biopsies with similar accuracy (all AUC comparisons P>0.05).ConclusionUrinary cell three-gene signature score may serve as a universal diagnostic signature of acute rejection due to TCMR, ABMR or MR in human kidney allografts with similar performance characteristics.

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“…As a result, monitoring strategies and therapeutic approaches for acute and chronic ABMR are heterogeneous and based on center practice. Rodriguez-Ramirez et al [8] discuss therapeutic approaches to minimize the risk of developing de- novo DSA, monitoring strategies, as well as treatments for ABMR.…”

mentioning

confidence: 99%