HLA‐specific memory B‐cell detection in kidney transplantation: Insights and future challenges

Wehmeier, Caroline; Karahan, Gonca E.; Heidt, Sebastiaan

doi:10.1111/iji.12493

Cited by 14 publications

(11 citation statements)

References 49 publications

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“…Donor human leukocyte antigen (HLA)-specific antibodies were initially identified as a major cause of ABMR. This type of DSA has been extensively studied and represents an established, “traditional” biomarker of ABMR, which is beyond the scope of this review [ 113 , 114 ].…”

Section: Armentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.

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Section: Armentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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“…Analyses on the molecular level of HLA disparities (i.e., eplet load and eplet immunogenicity) might provide better prediction, but such an evaluation would require a significantly larger number of cases (26)(27)(28)(29)(30). Another interesting approach could be the evaluation of memory B cell responses (31). With recent advances to detect memory B cells, it seems nowadays possible to obtain a more complete picture of the pre-transplant alloimmunization status in these women (32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Outcome of Husband-to-Wife Kidney Transplantation With Mutual Children: Single Center Experience Using T Cell-Depleting Induction and Review of the Literature

et al. 2021

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Few data on husband-to-wife transplantations with mutual children (H2W) exist in the current era. We investigated the outcome of H2W transplantations (n = 25) treated with T cell-depleting induction compared to women with prior pregnancies also receiving their first HLA-mismatched kidney transplant, but from a different donor source: (i) other living donor (n = 52) and (ii) deceased donor (n = 120). Seventy-four percent of the women had ≥2 pregnancies; median follow-up time was 5 years. Death-censored allograft survival was significantly lower in the H2W group compared to the other two groups (p = 0.03). Three of four graft losses in the H2W group were due to rejection. 5-year patient survival in the H2W group was high and similar compared to the other living donor group (100 vs. 98%; p = 0.28). The incidence of (sub)clinical antibody-mediated rejection was higher in the H2W group (36 vs. 20 vs. 18%) (p = 0.10). The frequency of infections was similar among the three groups. No immunological parameter was predictive for rejection or graft loss in H2W transplantations. In conclusion, H2W transplantation is a valuable option, but associated with a higher risk for allograft loss due to rejection despite T cell-depleting induction. Further research is required for better risk prediction on an individual patient level.

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“…Methods to detect HLA‐specific memory B cells refine the immunological risk assessment in patients with a history of alloantigen exposure 2 . There are a number of methods for HLA‐specific memory B cell detection 3 .…”

Section: Introductionmentioning

confidence: 99%

“…There are a number of methods for HLA‐specific memory B cell detection 3 . Among these, HLA antibody analysis in B cell culture supernatants is the only method allowing serum HLA antibody profiles to be directly compared with those of memory B cell‐derived HLA antibodies 2 …”

Section: Introductionmentioning

confidence: 99%

“…Methods to detect HLA‐specific memory B cells refine the immunological risk assessment in patients with a history of alloantigen exposure. 2 There are a number of methods for HLA‐specific memory B cell detection. 3 Among these, HLA antibody analysis in B cell culture supernatants is the only method allowing serum HLA antibody profiles to be directly compared with those of memory B cell‐derived HLA antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of different luminex single antigen bead kits for memory B cell‐derived HLA antibody detection

Karahan

Vaal

Bakker

et al. 2021

HLA

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Detection of HLA‐specific memory B cells can provide additional information on sensitization of alloantigen‐exposed individuals and refine immunological risk assessment. We have recently developed an assay enabling profiling of memory B cell‐derived HLA antibodies using luminex single antigen bead (SAB) assay. Here, we compared the performance of the SAB kits from two vendors for memory B cell‐derived HLA antibody detection. IgG was isolated from culture supernatants of polyclonally activated B cells from alloantigen‐exposed (n = 7) or nonexposed (n = 5) individuals, using our previously established method. Eluates containing isolated IgG from culture supernatants were tested for the presence of HLA antibodies using luminex SAB analysis from both One Lambda and Lifecodes (Immucor). In contrast to Lifecodes, high mean fluorescence intensity (MFI) signals were found for negative control beads in One Lambda (median MFI for class I:1730 and for class II:728), accompanied by high MFI values for self HLA‐coated beads, especially for HLA‐C. Despite high background in the One Lambda assays, 91% concordance for HLA class I and 85% concordance for HLA class II were found between the specificities detected using SAB kits from the two vendors. Our results show that HLA‐specific memory B cells can be profiled using kits from both vendors. However, when analyzing One Lambda results one should be aware of the restrictions related to nonspecific binding particularly in HLA‐C‐coated beads, and pay attention to self HLA‐coated beads in order to accurately identify the reactivities leading to the definition of the actual HLA antibody specificities.

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HLA‐specific memory B‐cell detection in kidney transplantation: Insights and future challenges

Cited by 14 publications

References 49 publications

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Outcome of Husband-to-Wife Kidney Transplantation With Mutual Children: Single Center Experience Using T Cell-Depleting Induction and Review of the Literature

Comparison of different luminex single antigen bead kits for memory B cell‐derived HLA antibody detection

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