Progress in kidney transplantation: The role for systems immunology

Abstract

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.

Clinical Research in Renal Transplantation: A Bibliometric Perspective on a Half-century of Innovation and Progress

“…Recent publication trends in top-notch RT research are indicating a remaining strong focus on immunology and immunosuppression. However, in contrast to the previous decades, dominated by RCTs comparing conventional drug combinations, recent publications point in the direction of precision medicine adopting approaches of system immunology, 39 multiomics techniques for monitoring, and novel personalized therapeutic strategies (eg, regulatory T-cell therapy). 40 Although this did not manifest clearly in our present data set, it is also expected that, due to its recent renaissance, xenotransplantation will represent a very significant field of research in the upcoming years.…”

Unveiling systemic responses in kidney transplantation: interplay between the allograft transcriptome and serum proteins

“…Data-driven experiments contrast many reductionist analyses in RTx ( 20 ) that link histology-based diagnosis with target molecules or outcomes ( 28 – 33 ). This study diverged from using the gold standard (Banff histological scoring) for clinical classification.…”

“…Great progress has been made in the Kidney Precision Medicine Project, which targets chronic kidney disease (CKD) and acute kidney injury using multidimensional phenotyping and computational modeling ( 18 , 19 ). In RTx, many omic technologies have been used to identify new gene signatures or biomarkers ( 20 ). A holistic perspective advocated by systems biology is only beginning to be adopted, and large RTx frameworks are missing ( 20 ).…”

“…In RTx, many omic technologies have been used to identify new gene signatures or biomarkers ( 20 ). A holistic perspective advocated by systems biology is only beginning to be adopted, and large RTx frameworks are missing ( 20 ). In this study, we hypothesized that the serum proteome is interconnected with the allograft via systemic immune responses.…”