Comparative analysis of how immune sensitization is defined prior to lung transplantation

Chin, Nicholas Chun Leong; Paraskeva, Miranda; Paul, Eldho; Cantwell, Linda; Levvey, Bronwyn; Williams, Trevor; Snell, Gregory I; Westall, Glen P.

doi:10.1016/j.humimm.2015.09.025

Cited by 8 publications

(3 citation statements)

References 21 publications

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“…Various studies suggest that the pre-transplant detection of circulating DSA is not associated with an increased risk of developing CLAD or related death if prospective cross-match testing was negative (11, 12). The pretransplant detection of DSA and antibodies directed againd non-HLA antigens such as angiotensin type 1 receptor (AT1R) and endothelin type A receptor (ETAR) is reported to have a negative impact on lung transplant outcome (13).…”

Section: Introductionmentioning

confidence: 99%

FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and Patients' Survival After Lung Transplant

et al. 2019

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Fc gamma receptors (FcγRs) play a major role in the regulation of humoral immune responses. Single-nucleotide polymorphisms (SNPs) of FCGR2A and FCGR3A can impact the expression level, IgG affinity and function of the CD32 and CD16 FcγRs in response to their engagement by the Fc fragment of IgG. The CD16 isoform encoded by FCGR3A [158V/V] controls the intensity of antibody-dependent cytotoxic alloimmune responses of natural killer cells (NK) and has been identified as a susceptibility marker predisposing patients to cardiac allograft vasculopathy after heart transplant. This study aimed to investigate whether FCGR2A and FCGR3A polymorphisms can also be associated with the clinical outcome of lung transplant recipients (LTRs). The SNPs of FCGR2A ([131R/H], rs1801274) and FCGR3A ([158V/F], rs396991) were identified in 158 LTRs and 184 Controls (CTL). The corresponding distribution of genotypic and allelic combinations was analyzed for potential links with the development of circulating donor-specific anti-HLA alloantibodies (DSA) detected at months 1 and 3 after lung transplant (LTx), the occurrence of acute rejection (AR) and chronic lung allograft dysfunction (CLAD), and the overall survival of LTRs. The FCGR3A [158V/V] genotype was identified as an independent susceptibility factor associated with higher rates of AR during the first trimester after LTx (HR 4.8, p < 0.0001, 95% CI 2.37–9.61), but it could not be associated with the level of CD16- mediated NK cell activation in response to the LTR's DSA, whatever the MFI intensity and C1q binding profiles of the DSA evaluated. The FCGR2A [131R/R] genotype was associated with lower CLAD-free survival of LTRs, independently of the presence of DSA at 3 months (HR 1.8, p = 0.024, 95% CI 1.08–3.03). Our data indicate that FCGR SNPs differentially affect the clinical outcome of LTRs and may be of use to stratify patients at higher risk of experiencing graft rejection. Furthermore, these data suggest that in the LTx setting, specific mechanisms of humoral alloreactivity, which cannot be solely explained by the complement and CD16-mediated pathogenic effects of DSA, may be involved in the development of acute and chronic lung allograft rejection.

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Section: Introductionmentioning

confidence: 99%

FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and Patients' Survival After Lung Transplant

et al. 2019

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“…Even if this were feasible, the extensive polymorphism of the HLA system would make an exact match (zero HLA mismatched donor-recipient) an extremely rare event [29]. The median number of HLA mismatches in lung transplantations on a scale of 0-6 has been shown to be 4 [30].…”

Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen Mismatch is Associated with Grade 3 Primary Graft Dysfunction at 72 Hours Following Bilateral Sequential Lung Transplantation: A Single-Center, Retrospective Cohort Study

Perry¹

2021

J Cardiol Res Rev Rep

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Background: The role of donor-recipient human leukocyte antigen (HLA) mismatch as a risk factor for developing primary graft dysfunction (PGD) after lung transplantation is not well understood. We describe a novel association between increased donor-recipient HLA mismatch and grade 3 PGD after bilateral lung transplantation. Methods: We retrospectively evaluated donor and recipient demographic data, co-morbidities, intraoperative interventions and outcomes in 99 consecutive adult patients undergoing primary bilateral lung transplantation. The primary outcome of this study was grade 3 PGD at 72 hours. Secondary outcomes included intensive care and hospital lengths of stay and mortality. Results: Eighteen patients (18%) met criteria for grade 3 PGD at 72 hours postoperatively. More non-Caucasian recipients (27.8% vs. 7.4%, p=0.026), and more patients with interstitial lung disease (72.2% vs 43.2%, p=0.031) developed grade 3 PGD. The use of inhaled epoprostenol (OR 4.38, 95% CI: 1.02-20.16, p=0.048), increased HLA mismatches (OR 2.85, 95% CI: 1.31-7.45, p=0.017) and the use of each 250mL unit of PRBCs during the intraoperative period (OR 0.77, 95% CI: 0.58-0.97, p=0.048) were independently associated with grade 3 PGD. Patients diagnosed with grade 3 PGD spent significantly longer time in the intensive care unit (22 days [6;74 days] vs. 7 days [2;83 days], p=<0.001) and hospital (30.5 days [10;83 days] vs. 18 days [3;97 days], p=0.012), and survival was significantly worse for those with PGD3 at 72 hours (log-rank p=0.009). Conclusion: Our data indicate, for the first time, that HLA donor-recipient mismatch is an independent risk factor for developing grade 3 PGD at 72 hours after bilateral lung transplantation.

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“…

Lung transplantation in the setting of preformed donor-specific antibodies (DSA) is frequently avoided due to the risk of hyperacute rejection, early antibody-mediated rejection, and earlier onset of chronic lung allograft dysfunction (CLAD). [1][2][3][4][5][6][7][8] Most lung transplant programs perform virtual crossmatching (VCM) at the time of a donor offer and usually decline an offer for a candidate if DSA are present or accept only if the DSA are felt to be "lower risk" on the basis of their mean fluorescent intensities (MFI), titers, or their cellbased crossmatch (CBCM) results. 9 However, declining donor lungs on the basis of DSA may disadvantage sensitized lung transplant

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mentioning

confidence: 99%

Long-term outcomes of sensitized lung transplant recipients after peri-operative desensitization

Aversa

Martinu

Patriquin

et al. 2021

American Journal of Transplantation

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Comparative analysis of how immune sensitization is defined prior to lung transplantation

Cited by 8 publications

References 21 publications

FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and Patients' Survival After Lung Transplant

FCGR3A and FCGR2A Genotypes Differentially Impact Allograft Rejection and Patients' Survival After Lung Transplant

Human Leukocyte Antigen Mismatch is Associated with Grade 3 Primary Graft Dysfunction at 72 Hours Following Bilateral Sequential Lung Transplantation: A Single-Center, Retrospective Cohort Study

Long-term outcomes of sensitized lung transplant recipients after peri-operative desensitization

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