Extracorporeal photopheresis as second‐line treatment therapy in life‐threatening primary graft dysfunction following lung transplantation

Robinson, C.; İnci, İlhan; Naegeli, Mirjam C.; Murer, Christian; Schuurmans, Macé M.; Urosevic-Maiwald, Mirjana; Schüpbach, Reto; Weder, Walter; Benden, Christian

doi:10.1111/petr.13145

Cited by 5 publications

(7 citation statements)

References 13 publications

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“…As previously prescribed ECP was successfully used for CLAD, 1,2 recurrent ACR 3 episodes and primary graft dysfunction 4 . We successfully treated idiopathic hyperammonemia and hypercapnic respiratory failure probably caused by toxic side‐effects of standard immunosuppression therapy early after lung transplantation using ECP as “second line” immunomodulation therapy in order to reduce standard immunosuppression.…”

Section: Discussion/summarymentioning

confidence: 98%

“…As previously prescribed ECP was successfully used for CLAD, 1,2 recurrent ACR 3 episodes and primary graft dysfunction. 4 We successfully treated idiopathic hyperammonemia and hypercapnic respiratory failure probably caused by toxic side-effects of standard immunosuppression therapy early after lung transplantation using ECP as "second line" immunomodulation therapy in order to reduce standard immunosuppression. Underlying triggering factors like glutamine synthetase deficiency by measuring normal plasma levels of glutamine, upregulation of glutamine synthetase or urease producing bacteria in blood and urine cultures were not found in our case.…”

Section: Discussion/summarymentioning

confidence: 99%

“…Extracorporeal photopheresis (ECP) is an accepted and safe “second‐line” treatment option in lung transplant recipients with chronic lung allograft dysfunction (CLAD) in order to stabilize lung allograft function 1,2 . In addition, our Group described the effective use of ECP in cases of recurrent acute cellular rejection (ACR) 3 and primary graft dysfunction (PGD) 4 . Here we illustrate a case of successful ECP usage as “second line” immunomodulatory therapy early after lung transplantation in a patient with idiopathic hyperammonemia in order to overcome toxic side‐effects of standard immunosuppressive therapy.…”

Section: Introductionmentioning

confidence: 99%

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ECP as additional immunomodulation in idiopathic hyperammonemia and recurrent hypercapnic respiratory failure early post lung transplantation

Steinack

Robinson

Nägeli

et al. 2020

J of Clinical Apheresis

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Extra-corporeal photopheresis (ECP) is known as safe ultimate treatment option for chronic lung allograft dysfunction (CLAD). Here, we report the first case of ECP as "second-line" immunomodulatory therapy early post-transplant in an adult patient undergoing lung transplantation for severe chronic thromboembolic pulmonary hypertension, complicated by impaired consciousness due to idiopathic hyperammonemia resulting in recurrent hypercapnic respiratory failure. ECP was initiated twice weekly on post-transplant day 25 and standard triple immunosuppression reduced. Within 2 weeks, the clinical status improved. ECP has been continued every 4 weeks after discharge. At 1 year post-transplant, ECP was stopped as maintenance immunosuppression was reached. We recommend to consider the immunomodulatory effect of ECP as "second line" immunomodulatory therapy in cases where standard immunosuppression causes severe collateral damage. ECP is able to assist prevention of allograft rejection in conjunction with reduced levels of standard immunosuppression, even in the early period following lung transplantation.

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Section: Discussion/summarymentioning

confidence: 98%

Section: Discussion/summarymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ECP as additional immunomodulation in idiopathic hyperammonemia and recurrent hypercapnic respiratory failure early post lung transplantation

Steinack

Robinson

Nägeli

et al. 2020

J of Clinical Apheresis

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“…Despite some available immunosuppressive treatments, patients with PGD still suffer from worsened conditions [35]. With the ultimate goal of uncovering additional therapeutic targets for PGD, this study investigated the underlying mechanism by which XIST affects PGD.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA X-inactive specific transcript silencing ameliorates primary graft dysfunction following lung transplantation through microRNA-21-dependent mechanism

Li¹,

Li²,

Han

et al. 2020

EBioMedicine

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Background: Primary graft dysfunction (PGD) is a known acute lung injury (ALI) and a major cause of fatality post-lung transplantation. Though some long non-coding RNAs (lncRNAs) have been studied in ALI through regulation of microRNAs (miRNAs), their effects on PGD remain undefined. The present study aims to explore the underlying mechanism of lncRNA X-inactive specific transcript (XIST) in PGD after lung transplantation. Methods: Initially, the expression of miR-21, IL-12A and XIST was determined by RT-qPCR and western blot analysis. The dual luciferase reporter assay, RNA pull-down and RIP assay were performed to identify the targeting relationship between miR-21 and IL-12A and the binding relationship between miR-21 and XIST. Loss-and gain-of-function investigations were conducted in rats treated with prolonged cold ischemia and polymorphonuclear neutrophils (PMNs). Findings: miR-21 was decreased, whilst XIST and IL-12A were increased in the bronchoalveolar lavage fluid of PGD patients after lung transplantation. Enhanced miR-21 expression in rats and PMNs resulted in downregulated expression of pro-inflammatory factors and chemokines, and enhanced the apoptosis of PMNs. XIST was found to upregulate IL-12A expression in a miR-21-dependent manner. Additionally, XIST silencing enhanced the apoptosis of PMNs and inhibited the neutrophil extracellular trap (NET) formation through upregulation of miR-21 but downregulation of IL-12A in vivo. Interpretation: In summary, lncRNA XIST upregulates IL-12A by binding to miR-21, thereby inducing NET formation and accelerating PGD after lung transplantation. This suggests that inhibition of XIST and NET may be beneficial for the treatment of PGD.

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“…Avoidance of potent or long-acting agents such as high-dose pulsed steroids, anti-thymocyte globulin or rituximab is critical. Photophoresis, although an expensive and uncommon therapy, may provide an efficacious and safe alternative mode of immunomodulation (14).…”

Section: Clear-cut Examples Include the Isolation Of Burkholderiamentioning

confidence: 99%

Review: immunosuppression for the lung transplant patient

Kotecha¹,

Ivulich²,

Snell³

2021

J Thorac Dis

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Lung transplantation (LTx) has evolved significantly since its inception and the improvement in LTx outcomes over the last three decades has predominantly been driven by advances in immunosuppression management. Despite the lack of new classes of immunosuppression medications, immunosuppressive strategies have evolved significantly from a universal method to a more targeted approach, reflecting a greater understanding of the need for individualized therapy and careful consideration of all factors that are influenced by immunosuppression choice. This has become increasingly important as the demographics of lung transplant recipients have changed over time, with older and more medically complex candidates being accepted and undergoing LTx. Furthermore, improved survival post lung transplant has translated into more immunosuppression related comorbidities long-term, predominantly chronic kidney disease (CKD) and malignancy, which has required further nuanced management approaches. This review provides an update on current traditional lung transplant immunosuppression strategies, with modifications based on preexisting recipient factors and comorbidities, peri-operative challenges and long term complications, balanced against the perpetual challenge of chronic lung allograft dysfunction (CLAD). As we continue to explore and understand the complexity of LTx immunology and the interplay of different factors, immunosuppression strategies will require ongoing critical evaluation and personalization in order to continue to improve lung transplant outcomes.

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Extracorporeal photopheresis as second‐line treatment therapy in life‐threatening primary graft dysfunction following lung transplantation

Cited by 5 publications

References 13 publications

ECP as additional immunomodulation in idiopathic hyperammonemia and recurrent hypercapnic respiratory failure early post lung transplantation

ECP as additional immunomodulation in idiopathic hyperammonemia and recurrent hypercapnic respiratory failure early post lung transplantation

Long non-coding RNA X-inactive specific transcript silencing ameliorates primary graft dysfunction following lung transplantation through microRNA-21-dependent mechanism

Review: immunosuppression for the lung transplant patient

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