Formation of donor‐specific antibodies depends on the epitope load of mismatched HLAs in lung transplant recipients: A retrospective single‐center study

Lobashevsky, Andrew L.; Niemann, Matthias; Kowinski, Brenda; Higgins, Nasra; AbdelWareth, Laila; Atrabulsi, Basel; Roe, David; Hage, Chadi A.

doi:10.1111/ctr.14755

Cited by 6 publications

(3 citation statements)

References 47 publications

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“…Among others, they incorporated the following features: estimated glomerular filtration rate, proteinuria, histology, and HLA antibody [42]. Furthermore, recently advanced approaches based on neural networks making use of large proteomic databases occurred for assessment of immunogenicity and probability to generate antibodies [27,43,44].…”

Section: Using ML For Cpmsmentioning

confidence: 99%

NephroCAGE—German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study

Schapranow,

Bayat,

Rasheed

et al. 2023

JMIR Res Protoc

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Background Recent advances in hardware and software enabled the use of artificial intelligence (AI) algorithms for analysis of complex data in a wide range of daily-life use cases. We aim to explore the benefits of applying AI to a specific use case in transplant nephrology: risk prediction for severe posttransplant events. For the first time, we combine multinational real-world transplant data, which require specific legal and technical protection measures. Objective The German-Canadian NephroCAGE consortium aims to develop and evaluate specific processes, software tools, and methods to (1) combine transplant data of more than 8000 cases over the past decades from leading transplant centers in Germany and Canada, (2) implement specific measures to protect sensitive transplant data, and (3) use multinational data as a foundation for developing high-quality prognostic AI models. Methods To protect sensitive transplant data addressing the first and second objectives, we aim to implement a decentralized NephroCAGE federated learning infrastructure upon a private blockchain. Our NephroCAGE federated learning infrastructure enables a switch of paradigms: instead of pooling sensitive data into a central database for analysis, it enables the transfer of clinical prediction models (CPMs) to clinical sites for local data analyses. Thus, sensitive transplant data reside protected in their original sites while the comparable small algorithms are exchanged instead. For our third objective, we will compare the performance of selected AI algorithms, for example, random forest and extreme gradient boosting, as foundation for CPMs to predict severe short- and long-term posttransplant risks, for example, graft failure or mortality. The CPMs will be trained on donor and recipient data from retrospective cohorts of kidney transplant patients. Results We have received initial funding for NephroCAGE in February 2021. All clinical partners have applied for and received ethics approval as of 2022. The process of exploration of clinical transplant database for variable extraction has started at all the centers in 2022. In total, 8120 patient records have been retrieved as of August 2023. The development and validation of CPMs is ongoing as of 2023. Conclusions For the first time, we will (1) combine kidney transplant data from nephrology centers in Germany and Canada, (2) implement federated learning as a foundation to use such real-world transplant data as a basis for the training of CPMs in a privacy-preserving way, and (3) develop a learning software system to investigate population specifics, for example, to understand population heterogeneity, treatment specificities, and individual impact on selected posttransplant outcomes. International Registered Report Identifier (IRRID) DERR1-10.2196/48892

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Section: Using ML For Cpmsmentioning

confidence: 99%

NephroCAGE—German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study

Schapranow,

Bayat,

Rasheed

et al. 2023

JMIR Res Protoc

Self Cite

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“…One study by Kulkarni and colleagues found an independent link between the growth of Pseudomonas aeruginosa, but not other organisms, on respiratory cultures and later development of DSAs, hypothesizing that the particularities of the immune response to Pseudomonas promotes an inflammatory milieu that promotes DSA formation ( 19 ). More recently, there has been considerable interest in the use of computer algorithms to estimate the risk of de novo DSA development on the basis of pre-transplant epitope mismatch loads ( 20 , 21 ).…”

Section: Clinical Implications Of Donor-specific Hla Antibodiesmentioning

confidence: 99%

Management of donor-specific antibodies in lung transplantation

Brandon,

Dunn,

Bollineni

et al. 2023

Front. Transplant.

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The formation of antibodies against donor human leukocyte antigens poses a challenging problem both for donor selection as well as postoperative graft function in lung transplantation. These donor-specific antibodies limit the pool of potential donor organs and are associated with episodes of antibody-mediated rejection, chronic lung allograft dysfunction, and increased mortality. Optimal management strategies for clearance of DSAs are poorly defined and vary greatly by institution; most of the data supporting any particular strategy is limited to small-scale retrospective cohort studies. A typical approach to antibody depletion may involve the use of high-dose steroids, plasma exchange, intravenous immunoglobulin, and possibly other immunomodulators or small-molecule therapies. This review seeks to define the current understanding of the significance of DSAs in lung transplantation and outline the literature supporting strategies for their management.

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“…PIRCHE II is a sophisticated implementation of this approach that generates a score for each donor antigen in the context of each recipient HLA class II allele, representing the number of unique, non-self, core sequences from the donor antigen that are expected to bind to and be presented by the recipient HLA (117). In just the past few years, PIRCHE II scores have been associated in studies of kidney, lung, cardiac, and liver transplant recipients with increased risk of DSA and TCMR (164)(165)(166)(167).…”

Section: Immunopeptidomementioning

confidence: 99%

Progress in kidney transplantation: The role for systems immunology

et al. 2022

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The development of systems biology represents an immense breakthrough in our ability to perform translational research and deliver personalized and precision medicine. A multidisciplinary approach in combination with use of novel techniques allows for the extraction and analysis of vast quantities of data even from the volume and source limited samples that can be obtained from human subjects. Continued advances in microfluidics, scalability and affordability of sequencing technologies, and development of data analysis tools have made the application of a multi-omics, or systems, approach more accessible for use outside of specialized centers. The study of alloimmune and protective immune responses after solid organ transplant offers innumerable opportunities for a multi-omics approach, however, transplant immunology labs are only just beginning to adopt the systems methodology. In this review, we focus on advances in biological techniques and how they are improving our understanding of the immune system and its interactions, highlighting potential applications in transplant immunology. First, we describe the techniques that are available, with emphasis on major advances that allow for increased scalability. Then, we review initial applications in the field of transplantation with a focus on topics that are nearing clinical integration. Finally, we examine major barriers to adapting these methods and discuss potential future developments.

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Formation of donor‐specific antibodies depends on the epitope load of mismatched HLAs in lung transplant recipients: A retrospective single‐center study

Cited by 6 publications

References 47 publications

NephroCAGE—German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study

NephroCAGE—German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study

Management of donor-specific antibodies in lung transplantation

Progress in kidney transplantation: The role for systems immunology

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