Preemptive treatment of de novo donor-specific antibodies in lung transplant patients reduces subsequent risk of chronic lung allograft dysfunction or death

Keller, Michael; Yang, Song; Ponor, Lucia; Bon, Ann Mary; Cochrane, A.; Philogene, Mary Carmelle; Bush, Errol L.; Shah, Pali D.; Matthews, Joby; Brown, Anne; Kong, Hyesik; Charya, Ananth V.; Luikart, Helen; Nathan, Steven D.; Khush, Kiran K.; Agbor‐Enoh, Sean

doi:10.1016/j.ajt.2022.12.019

Cited by 10 publications

(5 citation statements)

References 21 publications

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“…Hachem et al performed a prospective cohort study showing that patients who developed DSAs and received antibody-directed therapy had similar rates of CLAD and acute rejection as patients without DSAs [ 18 ]. Finally, in a recent multicenter retrospective analysis, Keller et al provided evidence that asymptomatic patients with dnDSAs who received preemptive treatment of any kind had a lower risk of CLAD or death than untreated patients with dnDSAs [ 19 ]. Based on these findings, it is meaningful to speculate that an active approach towards patients with dnDSAs could result in improved outcomes.…”

Section: Discussionmentioning

confidence: 99%

Impact of Transient and Persistent Donor-Specific Antibodies in Lung Transplantation

Auner,

Hillebrand,

Boehm

et al. 2024

Transpl Int

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Lung transplantation (LuTx) is an established treatment for patients with end-stage lung diseases, however, outcomes are limited by acute and chronic rejection. One aspect that has received increasing attention is the role of the host’s humoral alloresponse, particularly the formation of de novo donor-specific antibodies (dnDSAs). The aim of this study was to investigate the clinical significance of transient and persistent dnDSAs and to understand their impact on outcomes after LuTx. A retrospective analysis was conducted using DSA screening data from LuTx recipients obtained at the Medical University of Vienna between February 2016 and March 2021. Of the 405 LuTx recipients analyzed, 205 patients developed dnDSA during the follow-up period. Among these, 167 (81%) had transient dnDSA and 38 (19%) persistent dnDSA. Persistent but not transient dnDSAs were associated with chronic lung allograft dysfunction (CLAD) and antibody-mediated rejection (AMR) (p < 0.001 and p = 0.006, respectively). CLAD-free survival rates for persistent dnDSAs at 1-, 3-, and 5-year post-transplantation were significantly lower than for transient dnDSAs (89%, 59%, 56% vs. 91%, 79%, 77%; p = 0.004). Temporal dynamics of dnDSAs after LuTx have a substantial effect on patient outcomes. This study underlines that the persistence of dnDSAs poses a significant risk to graft and patient survival.

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Section: Discussionmentioning

confidence: 99%

Impact of Transient and Persistent Donor-Specific Antibodies in Lung Transplantation

Auner,

Hillebrand,

Boehm

et al. 2024

Transpl Int

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“…Furthermore, a subset of the untreated DSA positive cohort ultimately went on to develop clinical AMR and were treated at that time. Delaying therapy until clinical AMR was associated with a 3-fold increased risk of CLAD or death, and a shorter time to CLAD or deat (18.8 vs 22.9 months) overall suggesting that a preemptive treatment strategy is beneficial [161].…”

Section: Preemptive Treatment Sub Clinical Amrmentioning

confidence: 98%

“…The most common pre-emptive therapies included IVIG, IVIG + Rituximab, PLEX + IVIG + Rituximab. Pre-emptive DSA therapy was protective against a combined endpoint of CLAD or death, and clinical AMR [161]. Furthermore, a subset of the untreated DSA positive cohort ultimately went on to develop clinical AMR and were treated at that time.…”

Section: Preemptive Treatment Sub Clinical Amrmentioning

confidence: 98%

Acute Rejection of the Lung Allograft: Phenotypes and Management

Menachem,

Hanna,

Kulkarni

et al. 2023

OBM Transplant

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Treatment options for end stage lung diseases are limited to stabilizing lung failure, decreasing disease progression, and symptom management, but significant reversal of lost lung function is often not possible. For well selected patients, lung transplantation may be a viable option to improve both longevity and quality of life. Though outcomes for lung transplant recipients have improved over several decades, long term survival still lags behind that of other solid organ transplant recipients. Longevity after lung transplantation is limited by chronic lung allograft dysfunction. Numerous insults to the allograft contribute to chronic rejection, alloimmune injuries including acute T-cell mediated and antibody mediated rejection are chief among them. Therefore, monitoring for and management of acute cellular and antibody mediated rejection are of paramount importance to those caring for lung transplant recipients. We provide an up to date and comprehensive review of acute rejection affecting lung allografts and attempt to highlight pathophysiology, risk factors, clinical presentation, rejection phenotypes, management strategies, as well as related from of acute allograft injury.

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“…Next to preventive treatment, it is also important to treat underlying risk factors for CLAD development such as acute rejection and DSA development. Indeed, early targeted treatment for DSA in the absence of clinical signs and symptoms of antibody-mediated rejection (AMR), significantly increased CLAD-free and overall survival [29]. In that aspect, it is important to note that a randomized placebo-controlled trial with de-novo belatacept-based immunosuppression, aiming to reduce DSA development had to stop recruiting earlier because of an increased mortality.…”

Section: Chronic Lung Allograft Dysfunction Managementmentioning

confidence: 99%

The diagnosis and management of chronic lung allograft dysfunction

Verleden,

Hendriks,

Verleden

2024

Current Opinion in Pulmonary Medicine

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Purpose of review Chronic lung allograft dysfunction (CLAD) remains a life-threatening complication following lung transplantation. Different CLAD phenotypes have recently been defined, based on the combination of pulmonary function testing and chest computed tomography (CT) scanning and spurred renewed interests in differential diagnosis, risk factors and management of CLAD. Recent findings Given their crucial importance in the differential diagnosis, we will discuss the latest development in assessing the pulmonary function and chest CT scan, but also their limitations in proper CLAD phenotyping, especially with regards to patients with baseline allograft dysfunction. Since no definitive treatment exists, it remains important to timely identify clinical risk factors, but also to assess the presence of specific patterns or biomarkers in tissue or in broncho alveolar lavage in relation to CLAD (phenotypes). We will provide a comprehensive overview of the latest advances in risk factors and biomarker research in CLAD. Lastly, we will also review novel preventive and curative treatment strategies for CLAD. Summary Although this knowledge has significantly advanced the field of lung transplantation, more research is warranted because CLAD remains a life-threatening complication for all lung transplant recipients.

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Preemptive treatment of de novo donor-specific antibodies in lung transplant patients reduces subsequent risk of chronic lung allograft dysfunction or death

Cited by 10 publications

References 21 publications

Impact of Transient and Persistent Donor-Specific Antibodies in Lung Transplantation

Impact of Transient and Persistent Donor-Specific Antibodies in Lung Transplantation

Acute Rejection of the Lung Allograft: Phenotypes and Management

The diagnosis and management of chronic lung allograft dysfunction

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