The Presence of Pretransplant HLA Antibodies Does Not Impact the Development of Chronic Lung Allograft Dysfunction or CLAD-Related Death

Zazueta, Oscar E.; Preston, Sara; Moniodis, Anna; Fried, Sabrina; Kim, Min Ji; Townsend, Keri; Wood, Isabelle; Boukedes, Steve; Guleria, Indira; Camp, Phillip C.; El–Chemaly, Souheil; Rosas, Iván O.; Chandraker, Anil; Milford, Edgar L.; Goldberg, Hilary J.

doi:10.1097/tp.0000000000001494

Cited by 16 publications

(12 citation statements)

References 16 publications

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“…Bharat et al reported that PGD is associated with an inflammatory cascade that augments the anti-HLA response that predisposes patients to BOS. Based on many previous studies as well as the results of this study, an immunological response may be one of the mechanisms among the multifactorial causes of PGD [26]. Similar results have been reported for other solid organ transplant types.…”

Section: Discussionsupporting

confidence: 89%

Prevalence of pre-transplant anti-HLA antibodies and their impact on outcomes in lung transplant recipients

Park

Lee

Choi

et al. 2016

8.2 Transplantation

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Background: Previous studies have suggested that antibodies against human leukocyte antigen (HLA) are associated with worse outcomes in lung transplantation. However, little is known about the factors associated with outcomes following lung transplantation in Asia. Accordingly, we investigated the prevalence of anti-HLA antibodies in recipients before transplantation and assessed their impact on outcomes in Korea. Methods: A single-center retrospective study was conducted. The study included 76 patients who received a lung transplant at a tertiary hospital in South Korea between January 2010 and March 2015. Results: Nine patients (11.8%) had class I and/or class II panel-reactive antibodies greater than 50%. Twelve patients (15.8%) had anti-HLA antibodies with a low mean fluorescence intensity (MFI, 1000-3000), 7 (9.2%) with a moderate MFI (3000-5000), and 12 (15.8%) with a high MFI (> 5000). Ten patients (13.2%) had suspected donor-specific antibodies (DSA), and 60% (6/10) of these patients had antibodies with a high MFI. In an analysis of outcomes, high-grade (≥2) primary graft dysfunction (PGD) was more frequent in patients with anti-HLA antibodies with moderate-to-high MFI values than in patients with low MFI values (39.4% vs. 14.0%, p = 0.011). Of 20 patients who survived longer than 2 years and evaluated for pBOS after transplant, potential bronchiolitis obliterans syndrome (pBOS) or BOS was more frequent in patients with anti-HLA antibodies with moderate-to-high MFI than in patients with low MFI, although this difference was not statistically significant (50.0% vs. 14.3%, p = 0.131). Conclusions: The prevalence of anti-HLA antibodies with high MFI was not high in Korea. However, the MFI was relatively high in patients with DSA. Anti-HLA antibodies with moderate-to-high MFI values were related to highgrade PGD. Therefore, recipients with high MFI before lung transplantation should be considered for desensitization and close monitoring.

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Section: Discussionsupporting

confidence: 89%

Prevalence of pre-transplant anti-HLA antibodies and their impact on outcomes in lung transplant recipients

Park

Lee

Choi

et al. 2016

8.2 Transplantation

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Section: Discussionmentioning

confidence: 87%

“…Luminex assay is more sensitive than the conventional CDC method [ 23 – 25 ]. A recent report by Goldberg et al on the basis of results using Luminex assays showed that 30% of subjects had circulating class I HLA antibodies alone, 4% Class II, and 14.4% class I and class II at MFI > 1000 [ 26 ]. According to Chung et al, of 129 patients who were waiting for a kidney transplant in Korea, 56 patients (43.4%) had PRA ≥ 20% by solid phase Luminex PRA, 45 patients (34.9%) had anti-HLA antibodies based on a Luminex single antigen assay, and 25 patients (44.6%) had HLA-DSA [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of pre-transplant anti-HLA antibodies and their impact on outcomes in lung transplant recipients

et al. 2018

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BackgroundPrevious studies have suggested that antibodies against human leukocyte antigen (HLA) are associated with worse outcomes in lung transplantation. However, little is known about the factors associated with outcomes following lung transplantation in Asia. Accordingly, we investigated the prevalence of anti-HLA antibodies in recipients before transplantation and assessed their impact on outcomes in Korea.MethodsA single-center retrospective study was conducted. The study included 76 patients who received a lung transplant at a tertiary hospital in South Korea between January 2010 and March 2015.ResultsNine patients (11.8%) had class I and/or class II panel-reactive antibodies greater than 50%. Twelve patients (15.8%) had anti-HLA antibodies with a low mean fluorescence intensity (MFI, 1000–3000), 7 (9.2%) with a moderate MFI (3000–5000), and 12 (15.8%) with a high MFI (> 5000). Ten patients (13.2%) had suspected donor-specific antibodies (DSA), and 60% (6/10) of these patients had antibodies with a high MFI. In an analysis of outcomes, high-grade (≥2) primary graft dysfunction (PGD) was more frequent in patients with anti-HLA antibodies with moderate-to-high MFI values than in patients with low MFI values (39.4% vs. 14.0%, p = 0.011). Of 20 patients who survived longer than 2 years and evaluated for pBOS after transplant, potential bronchiolitis obliterans syndrome (pBOS) or BOS was more frequent in patients with anti-HLA antibodies with moderate-to-high MFI than in patients with low MFI, although this difference was not statistically significant (50.0% vs. 14.3%, p = 0.131).ConclusionsThe prevalence of anti-HLA antibodies with high MFI was not high in Korea. However, the MFI was relatively high in patients with DSA. Anti-HLA antibodies with moderate-to-high MFI values were related to high-grade PGD. Therefore, recipients with high MFI before lung transplantation should be considered for desensitization and close monitoring.

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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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The Presence of Pretransplant HLA Antibodies Does Not Impact the Development of Chronic Lung Allograft Dysfunction or CLAD-Related Death

Cited by 16 publications

References 16 publications

Prevalence of pre-transplant anti-HLA antibodies and their impact on outcomes in lung transplant recipients

Prevalence of pre-transplant anti-HLA antibodies and their impact on outcomes in lung transplant recipients

Prevalence of pre-transplant anti-HLA antibodies and their impact on outcomes in lung transplant recipients

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

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