Impact of Pretransplant Anti-HLA Antibodies on Outcomes in Lung Transplant Candidates

Kim, Min Ji; Townsend, Keri; Wood, Isabelle; Boukedes, Steve; Guleria, Indira; Gabardi, Steven; El–Chemaly, Souheil; Camp, Phillip C.; Chandraker, Anil; Milford, Edgar L.; Goldberg, Hilary J.

doi:10.1164/rccm.201312-2160oc

Cited by 67 publications

(62 citation statements)

References 22 publications

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“…Indeed, pre-transplant DSA may not be detected by less sensitive assays, yet these antibodies are associated with an increased risk of CLAD and death after transplantation (20, 21). Furthermore, our findings corroborate the results of the analysis of the modern era in the UNOS registry and a recent single-center study that used a solid-phase antibody detection assay (14, 22). Our data extend these results by demonstrating that there is no association between pre-transplant allosensitization and ACR, LB, CLAD, and long-term graft survival.…”

Section: Discussionsupporting

confidence: 88%

The impact of pre-transplant allosensitization on outcomes after lung transplantation

Bosanquet

Witt

Bemiss

et al. 2015

The Journal of Heart and Lung Transplantation

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Background Allosensitization can be a significant barrier to transplantation for some patients, and previous studies suggested that pre-transplant allosensitization was associated with worse outcomes after lung transplantation. However, human leukocyte antigen (HLA) antibody testing has evolved significantly over the past 10 years and current assays are highly sensitive and specific. Methods We examined the impact of pre-transplant allosensitization on post-transplant outcomes in the era of solid-phase multiplex HLA antibody detection assays in this retrospective, single-center study of 304 adult recipients between 1/1/2006 and 12/31/2012. We accepted donor organs for allosensitized patients if a virtual crossmatch was compatible with all previously identified antibodies. Results In univariate and multivariate Cox proportional hazards models, pre-transplant allosensitization, the calculated panel reactive antibody (CPRA), and the number of pre-transplant HLA antibodies were not associated with the development of acute cellular rejection, lymphocytic bronchiolitis, donor-specific HLA antibodies, chronic lung allograft dysfunction, or graft failure. Conclusions We conclude that pre-transplant allosensitization does not adversely affect outcomes after lung transplantation when the potentially reactive HLA are avoided in the donor by a virtual crossmatch with the recipient.

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Section: Discussionsupporting

confidence: 88%

The impact of pre-transplant allosensitization on outcomes after lung transplantation

Bosanquet

Witt

Bemiss

et al. 2015

The Journal of Heart and Lung Transplantation

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“…Moreover, the cutoff for avidity of antibodies [measured using mean fluorescence intensity (MFI)] varies among centers, and this introduces additional variability in the detection of HLA antibodies. In a retrospective cohort study of 63 recipients who either had a calculated panel reactive antibody (cPRA) ≥ 50% or DSA, those who had an MFI ≥ 3000 had a significantly higher incidence of AMR compared to those with an MFI < 3000 (35). Hence, a higher cutoff (e.g., 5000) increases the risk of missing potentially pathogenic antibodies on VXM (36, 37).…”

Section: Pathogenesis Of Amrmentioning

confidence: 99%

Antibody-Mediated Rejection in Lung Transplantation

Kulkarni

Bemiss²,

Hachem

2015

Curr Transpl Rep

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There has been increasing awareness of antibody-mediated rejection (AMR) as an important cause of graft failure after lung transplantation in recent years. However, the diagnostic criteria for pulmonary AMR are not well defined. All four tenets of AMR in kidney and heart transplantation, graft dysfunction, complement component deposition, circulating donor-specific antibodies (DSA), and histopathologic changes consistent with AMR, are infrequently present in lung transplantation. Nonetheless, the lung transplant community has made important progress recognizing cases of AMR and developing a definition. However, AMR is often refractory to therapy resulting in graft failure and death. In this review, we discuss the progress and challenges in the diagnosis and therapeutic options for pulmonary AMR. In addition, we briefly examine emerging paradigms of C4d-negative AMR and chronic AMR, and conclude that significant progress is needed to mitigate the effects of humoral immune responses after lung transplantation.

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“…[7][8][9][10] This was further demonstrated using single antigen flow beads (SAFB) assays which greatly improved the resolution and the sensitivity of donor-specific antibodies (DSA) detection. [11][12][13][14][15][16] However, detection of serum DSA with SAFB has technical limitations, falsenegative and false-positive results being respectively caused by complement interference [17][18][19] and by anti-HLA antibodies of ill-defined pathogenic role recognizing denatured class I HLA molecules. [20][21][22][23][24][25] The presence of DSA is not synonymous with lung allograft injury.…”

Section: Introductionmentioning

confidence: 99%

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

Visentin

Chartier

Massara

et al. 2016

The Journal of Heart and Lung Transplantation

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Impact of Pretransplant Anti-HLA Antibodies on Outcomes in Lung Transplant Candidates

Abstract: The presence of anti-HLA antibodies at the high MFI threshold (>3,000) was associated with lower transplant rate and higher rates of AMR. Screening for anti-HLA antibodies using the 3,000 MFI threshold may be important in managing transplant candidates and recipients.

Cited by 67 publications

References 22 publications

The impact of pre-transplant allosensitization on outcomes after lung transplantation

The impact of pre-transplant allosensitization on outcomes after lung transplantation

Antibody-Mediated Rejection in Lung Transplantation

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

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