Cutoff values and data handling for solid-phase testing for antibodies to HLA: Effects on listing unacceptable antigens for thoracic organ transplantation

Liu, Chang; Wetter, Lauren; Pang, Shuchao; Phelan, D.; Mohanakumar, Thalachallour; Morris, Gerald P.

doi:10.1016/j.humimm.2012.04.016

Cited by 24 publications

(13 citation statements)

References 23 publications

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“…It is relevant that in the former study, C3d binding was reported in one‐third of sera with low‐ or medium‐MFI DSAs, whereas in our cohort, all dn DSAs that were found to bind C3d had MFI values >8000 with >80% of C3d + dn DSAs displaying MFI values >14 000. The apparent discrepancy in MFI values is likely due to the measures taken in our study to preclude the prozone effect and to the presence of at least 30% of patients with C3d + anti‐HLA class I DSAs in the adult cohort that has been reported to be able to fix complement in a CDC assay at lower MFI .…”

Section: Discussionmentioning

confidence: 82%

Acquisition of C3d‐Binding Activity by De Novo Donor‐Specific HLA Antibodies Correlates With Graft Loss in Nonsensitized Pediatric Kidney Recipients

Comoli

Cioni

Tagliamacco

et al. 2016

American Journal of Transplantation

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These authors contributed equally to this work.Alloantibody-mediated graft injury is a major cause of kidney dysfunction and loss. The complementbinding ability of de novo donor-specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complementfixing dnDSAs and their role in antibody-mediated rejection development and graft loss. A total of 114 pediatric nonsensitized recipients of first kidney allograft were periodically monitored for dnDSAs using flow bead assays, followed by C3d and C1q assay in case of positivity. Overall, 39 patients developed dnDSAs, which were C1q + and C3d + in 25 and nine patients, respectively. At follow-up, progressive acquisition over time of dnDSA C1q and C3d binding ability, within the same antigenic specificity, was observed, paralleled by an increase in mean fluorescence intensity that correlated with clinical outcome. C3d-fixing dnDSAs were better fit to stratify graft loss risk when the different dnDSA categories were evaluated in combined models because the 10-year graft survival probability was lower in patients with C3d-binding dnDSA than in those without dnDSAs or with C1q + /C3d À or non-complement-binding dnDSAs (40% vs. 94%, 100%, and 100%, respectively). Based on the kinetics profile, we favor dnDSA removal or modulation at first confirmed positivity, with treatment intensification guided by dnDSA biological characteristics.

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Section: Discussionmentioning

confidence: 82%

Acquisition of C3d‐Binding Activity by De Novo Donor‐Specific HLA Antibodies Correlates With Graft Loss in Nonsensitized Pediatric Kidney Recipients

Comoli

Cioni

Tagliamacco

et al. 2016

American Journal of Transplantation

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“…For lung transplant recipients no official statement exist defining unacceptable antigens and their therapeutic consequence in immunized patients before transplantation as well algorithm for post‐transplant monitoring of HLA‐antibodies after transplantation . Liu et al showed cut‐off values and data handling for solid‐phase testing for HLA‐antibodies to validate the use of SPA in virtual crossmatch for thoracic organ transplantation . Both pre‐ and post‐transplant risk assessment for lung transplantation are center‐specific and vary between the transplant centers worldwide.…”

Section: Discussionmentioning

confidence: 99%

Bronchiolitis obliterans syndrome due to donor‐specific HLA‐antibodies

et al. 2015

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Chronic lung allograft dysfunction (CLAD) is a limiting factor for long-term survival in lung transplant recipients. Donor-specific human leukocyte antigen (HLA)-antibodies (DSA) have been suggested as potential risk factors for CLAD. However, their impact on clinical outcome following lung transplantation remains controversial. We performed a single-center study of 120 lung transplant recipients transplanted between 2006 and 2011. Patient sera were investigated before and after transplantation. The sera were screened by means of Luminex(®) technology (Luminex Inc., Austin, TX, USA) for IgG-HLA-class I and class II antibodies (ab). Using single antigen beads, DSA were identified and correlated retrospectively with clinical parameters. After transplantation 39 out of 120 patients (32.5%) were positive for HLA-ab. The incidence of de novo DSA formation was 27 of 120 patients (22.5%). Eleven of 27 (41%) of de novo DSA-positive patients developed BOS compared to 13 of 93 (14%) DSA-negative patients (p = 0.002). Furthermore, the generation of de novo DSA was independently associated with the development of BOS in multivariable analysis [hazard ration (HR) 2.5, 95% confidence interval (CI) 1.0-6.08; p = 0.046). Our results indicate that de novo DSA are associated with the development of BOS after lung transplantation. Monitoring of HLA-ab after transplantation is useful for identifying high-risk patients and offers an opportunity for early therapeutic intervention.

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“…The beads are then washed against a fluoro-labelled anti-human IgG antibody, which provides a mean fluorescence intensity (MFI) representing the amount of fluoro-labelled anti-IgG in complex with anti-HLA antibody. The MFI is not an accurate quantitative measurement of the amount of antibody concentration which requires measurement of the antibody titre (108)(109)(110).…”

Section: Diagnosis Of Amrmentioning

confidence: 99%

Acute rejection

Benzimra¹,

Calligaro²,

Glanville³

2017

J. Thorac. Dis.

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Despite induction immunosuppression and the use of aggressive maintenance immunosuppressive regimens, acute allograft rejection following lung transplantation is still a problem with important diagnostic and therapeutic challenges. As well as causing early graft loss and mortality, acute rejection also initiates the chronic alloimmune responses and airway-centred inflammation that predispose to bronchiolitis obliterans syndrome (BOS), also known as chronic lung allograft dysfunction (CLAD), which is a major source of morbidity and mortality after lung transplantation. Cellular responses to human leukocyte antigens (HLAs) on the allograft have traditionally been considered the main mechanism of acute rejection, but the influence of humoral immunity is increasingly recognised. As with other several other solid organ transplants, antibody-mediated rejection (AMR) is now a well-accepted and distinct clinical entity in lung transplantation. While acute cellular rejection (ACR) has defined histopathological criteria, transbronchial biopsy is less useful in AMR and its diagnosis is complicated by challenges in the measurement of antibodies directed against donor HLA, and a determination of their significance. Increasing awareness of the importance of non-HLA antigens further clouds this issue. Here, we review the pathophysiology, diagnosis, clinical presentation and treatment of ACR and AMR in lung transplantation, and discuss future potential biomarkers of both processes that may forward our understanding of these conditions.

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Cutoff values and data handling for solid-phase testing for antibodies to HLA: Effects on listing unacceptable antigens for thoracic organ transplantation

Cited by 24 publications

References 23 publications

Acquisition of C3d‐Binding Activity by De Novo Donor‐Specific HLA Antibodies Correlates With Graft Loss in Nonsensitized Pediatric Kidney Recipients

Acquisition of C3d‐Binding Activity by De Novo Donor‐Specific HLA Antibodies Correlates With Graft Loss in Nonsensitized Pediatric Kidney Recipients

Bronchiolitis obliterans syndrome due to donor‐specific HLA‐antibodies

Acute rejection

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