Lung intragraft donor-specific antibodies as a risk factor for graft loss

Visentin, Jonathan; Chartier, Albane; Massara, Layal; Linares, Gabriel; Guidicelli, Gwendaline; Blanchard, Élodie; Parrens, Marie; Bégueret, Hugues; Dromer, C.; Taupin, Jean‐Luc

doi:10.1016/j.healun.2016.06.010

Cited by 41 publications

(46 citation statements)

References 42 publications

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“…Multiple individual studies, however, reported a stronger link between CLAD and survival with higher MFI antibodies as well as dnDSA associated with concurrent AMR. 7,11,13,16 Third, both pre-and post-transplant screening intervals showed significant variability. Studies with less frequent pre-transplant screens may have overestimated the incidence of dnDSA since antibodies identified as de novo posttransplant may have been missed pre-transplant because of limited screening and potential sensitization events.…”

Section: Discussionmentioning

confidence: 95%

“…Because there was no clear way of aggregating centers by MFI threshold, we could not assess the impact of utilizing higher MFI cut‐offs on the prevalence of dnDSA development or on the correlation between higher MFI and organ and patient survival. Multiple individual studies, however, reported a stronger link between CLAD and survival with higher MFI antibodies as well as dnDSA associated with concurrent AMR …”

Section: Discussionmentioning

confidence: 98%

“…There remains significant program‐to‐program variability in the approach to detection and management of HLA antibodies in candidates and recipients. As a result, the reported prevalence of pre‐transplant HLA antibodies ranges from 10.8% to 44.0% and the incidence of post‐transplant dnDSA ranges from 12.2% to 61.2% . It is unknown whether these epidemiologic differences are due to antibody‐detection methods, immunosuppression use, monitoring protocols, or patient demographics.…”

Section: Introductionmentioning

confidence: 99%

“…As a result, the reported prevalence of pre-transplant HLA antibodies ranges from 10.8% to 44.0% and the incidence of posttransplant dnDSA ranges from 12.2% to 61.2%. [5][6][7][8][9][10][11][12][13][14][15][16] It is unknown whether these epidemiologic differences are due to antibody-detection methods, immunosuppression use, monitoring protocols, or patient demographics.…”

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confidence: 99%

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Detection and clinical impact of human leukocyte antigen antibodies in lung transplantation: A systematic review and meta‐analysis

Courtwright

Diamond

Wood

et al. 2017

HLA

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There is significant variability in lung transplant centers' approach to HLA antibodies, creating heterogeneity regarding their clinical significance. Some institutions use beads coated with multiple HLA to screen candidate sera and then use single antigen bead (SAB) to determine antibody identity if the pre-screen is positive. Other centers do not pre-screen, using SAB alone, which may detect low-level antibodies of unknown significance. The primary objective of this study was to review the current literature to identify sources of heterogeneity in the identification of pre- and post-lung transplant HLA antibodies, particularly regarding antibody-detection methods. A random effects model meta-analysis was used to evaluate the relationship between pre-transplant HLA antibodies and the development of de novo donor-specific antibodies (dnDSA) and dnDSA and chronic lung allograft dysfunction (CLAD). Each outcome was stratified by the method of antibody detection (pre-screen followed by SAB vs SAB alone). We identified 13 cohort studies with a total of 3039 patients. The use of pre-screening followed by SAB testing and the use of induction immunosuppression were associated with lower prevalence of dnDSA. Patients with pre-transplant HLA antibodies were more likely to develop dnDSA (hazard ratio [HR] = 1.49, 95% confidence interval [CI]: 1.19-1.86, P < .001). dnDSA was associated with CLAD (HR = 2.02, 95% CI = 1.37-2.97, P < .001). When considering studies using SAB alone, however, pre-transplant antibody status was no longer associated with dnDSA and dnDSA was no longer associated with CLAD. Based on the current literature, SAB-alone testing may detect less clinically relevant antibodies than pre-screening followed by SAB.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Detection and clinical impact of human leukocyte antigen antibodies in lung transplantation: A systematic review and meta‐analysis

Courtwright

Diamond

Wood

et al. 2017

HLA

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“…Donor and recipient HLA‐typing is also essential in pre‐ and post‐transplant monitoring in order to precisely identify donor‐specific antibodies (DSA). Indeed, preformed and de novo DSA are associated with graft rejection, dysfunction, and loss . The link between DSA and graft outcomes has been particularly emphasized because the development of Single Antigen Flow Beads assays that, for now, allows humoral reactivity against around 200 class‐I and ‐II HLA antigens to be studied.…”

Section: Introductionmentioning

confidence: 99%

Improvement in HLA‐typing by new sequence‐specific oligonucleotides kits for HLA‐A, ‐B, and ‐DRB1 loci

Bouthemy

Ralazamahaleo

Jollet

et al. 2018

HLA

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Polymerase chain reaction sequence-specific oligonucleotide is commonly used for HLA-typing. We replaced our LabType SSO HD (HD) kits with LabType SSO XR (XR) kits (One Lambda, Inc., Canoga Park, California) for HLA-A, -B, and -DRB1 following acquisition of a LABScan3D analyzer. The XR kits have more bead regions than the HD kits, allowing for an extended number of probes and exon coverage. They are claimed to improve typing resolution and to diminish the number of allele ambiguities, including common and well-documented (CWD) and null alleles to be resolved. We retrospectively selected patients who had their first HLA-typing performed with the HD kits and their second determination with the XR kits between 2015 and 2016. Forty-two patients were selected for HLA-A typing comparison, and 48 for HLA-B and 41 for HLA-DRB1. XR kits significantly decreased the number of allele ambiguities for HLA-A and -B. On the other hand, the improvement was limited for the HLA-DRB1 locus. The XR kits did not resolve all the CWD HLA allele ambiguities, which may be important for organ and/or hematopoietic stem cell transplantations. The XR kits eliminated 88%, 62%, and 27% of null allele ambiguities for HLA-A, -B, and -DRB1 loci, respectively. In conclusion, the XR kits allow for a significant improvement of HLA-typing resolution for HLA-A and -B loci in comparison with HD kits. In contrast, the number of oligonucleotides in the XR HLA-DRB1 kit should be extended to include exon 3 at the very least. It could also be interesting to include oligonucleotides allowing HLA-DRB3, 4, and 5 typing.

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HLA and lung transplantation

Suberbielle

et al. 2019

Front. Med.

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Lung transplantation is increasingly practiced for patients with end-stage lung disease. The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies, mainly directed against the protein products of the HLA complex of the organ donor. While the association between antibody mediated rejection and allograft damage has been well established in renal and heart transplantation, it has not yet been well characterized in lung transplantation. This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class I and II antigens. The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or de novo posttransplant circulating antibodies. Finally, potential mechanisms, which may act individually or in combination, of antibody mediated damage to solid organ transplants are considered.

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Lung intragraft donor-specific antibodies as a risk factor for graft loss

Abstract: In lung transplantation, gDSA appears to be a valuable biomarker to identify pathogenic DSA and LTRs with a higher risk for graft loss.

Cited by 41 publications

References 42 publications

Detection and clinical impact of human leukocyte antigen antibodies in lung transplantation: A systematic review and meta‐analysis

Detection and clinical impact of human leukocyte antigen antibodies in lung transplantation: A systematic review and meta‐analysis

Improvement in HLA‐typing by new sequence‐specific oligonucleotides kits for HLA‐A, ‐B, and ‐DRB1 loci

HLA and lung transplantation

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