Risk factors for chronic lung allograft dysfunction (CLAD) in the SysCLAD cohort

Koutsokera, Angela; Royer, Pierre-Joseph; Fritz, Andreas; Benden, Christian; Tissot, A. N.; Aubert, John-David; Antonietti, Jean‐Philippe; Botturi-Cavaillès, K.; Magnan, A.; Pison, Christophe; Nicod, Laurent

doi:10.1183/13993003.congress-2015.pa1800

Cited by 4 publications

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“…Our methodology and findings are reported in accordance with the TRIPOD recommendations ( 15 ). Some of the results of this study have been previously reported as conference abstracts ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 60%

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

Koutsokera¹,

Royer²,

Antonietti³

et al. 2017

Front. Med.

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BackgroundChronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described.MethodsLT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis.ResultsAmong patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS.ConclusionAlthough these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach.

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Section: Introductionmentioning

confidence: 60%

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

Koutsokera¹,

Royer²,

Antonietti³

et al. 2017

Front. Med.

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“…185 Moreover, the underlying diagnosis and immunosuppression regimens have been recently described as specific risk factors for RAS. 186 Further works will be needed to confirm these data and precisely define the specificities and similarities between the 2 diseases. Noteworthy, some evidences presented in this review have been collected before the description of RAS, that is, on chronic rejection groups where BOS and RAS patients were presumably pooled.…”

Section: Discussionmentioning

confidence: 95%

Chronic Lung Allograft Dysfunction

et al. 2016

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Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.

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“…In this study, we have focused solely on the alloimmune-related mechanisms. (Chronic) rejection may be just a small fraction of CLAD, alongside injury driven by non-alloimmune factors, such as infections, reflux and environmental factors like pollution and smoking [41]. The latter directly cause damage to the epithelium and/or endothelium, contributing to chronic inflammation and thereby facilitating allorecognition [42].…”

Section: Discussionmentioning

confidence: 99%

The Immunopathology of Pulmonary Rejection after Murine Lung Transplantation

Kaes,

Pollenus,

Hooft

et al. 2024

Cells

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To improve outcomes following lung transplantation, it is essential to understand the immunological mechanisms that result in chronic graft failure. The associated clinical syndrome is termed chronic lung allograft dysfunction (CLAD), which is known to be induced by alloimmune-dependent (i.e., rejection) and alloimmune-independent factors (e.g., infections, reflux and environmental factors). We aimed to explore the alloimmune-related mechanism, i.e., pulmonary rejection. In this study, we use a murine orthotopic left lung transplant model using isografts and allografts (C57BL/6 or BALB/c as donors to C57BL/6 recipients), with daily immunosuppression (10 mg/kg cyclosporin A and 1.6 mg/kg methylprednisolone). Serial sacrifice was performed at days 1, 7 and 35 post-transplantation (n = 6 at each time point for each group). Left transplanted lungs were harvested, a single-cell suspension was made and absolute numbers of immune cells were quantified using multicolor flow cytometry. The rejection process followed the principles of a classic immune response, including innate but mainly adaptive immune cells. At day 7 following transplantation, the numbers of interstitial macrophages, monocytes, dendritic cells, NK cells, NKT cells, CD4+ T cells and CD8+ T and B cells were increased in allografts compared with isografts. Only dendritic cells and CD4+ T cells remained elevated at day 35 in allografts. Our study provides insights into the immunological mechanisms of true pulmonary rejection after murine lung transplantation. These results might be important in further research on diagnostic evaluation and treatment for CLAD.

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Risk factors for chronic lung allograft dysfunction (CLAD) in the SysCLAD cohort

Cited by 4 publications

References 0 publications

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

Chronic Lung Allograft Dysfunction

The Immunopathology of Pulmonary Rejection after Murine Lung Transplantation

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