Solid organ transplantation has become the optimal and often the only viable treatment for end stage organ disease. The advent of potent immunosuppression resulted in significant improvement in short-term outcomes of solid organ recipients, with low rates of early rejection. However, the long-term outcomes have not meaningfully changed over the last 30 years, as most solid organ transplants are lost prematurely, resulting in increased mortality and morbidity for the recipients and high costs to the health care systems. The most prevalent cause of premature solid organ transplant loss is antibody-mediated rejection. It follows that improved therapies to abort the effects of alloimmune attack on the graft may be able to prevent premature graft loss.

The pathophysiology of antibody-mediated rejection is not completely understood, but it is mainly attributed to donor-specific antibodies directed against the human leukocyte antigens (HLA) on the graft endothelium. Evidence shows that these donor-specific antibodies are able to activate complement and antibody-dependent cell cytotoxicity on natural killer and myeloid cells. However, the presence of donor-specific antibodies does not always translate into rejection, as 30-60% of kidney transplant recipients have antibodies but no evidence of clinical or subclinical rejection. Perplexingly, about half of all kidney transplant recipients with antibody-mediated rejection do not have historic or concurrent donor-specific antibodies. The understanding of the causes and mechanisms of rejection remains incomplete, and this knowledge gap is responsible, at least in part, for the lack of effective therapies for preventing or ameliorating antibody-mediated rejection.

The emergence of multi-omics approaches, including single-cell and bulk RNA sequencing, proteomics, metabolomics, and ever evolving computational methods to integrate and analyze the tissue molecular data combined with granular clinical data, opens the door for precision medicine approaches and potential identification of novel therapeutic targets for treatment of alloimmune injury, including antibody-mediated rejection.

In this Research Topic, we aim to bring to light studies that explore high-throughput methodologies in solid organ transplantation, with the goal of identifying novel therapeutic targets for alloimmune injury. We invite Original Research, Review, and Perspective articles focusing on, but not limited to, the following topics in the field of solid organ transplantation:

• Single cell-based and bulk omics methods including genomics, transcriptomics, proteomics, and metabolomics focused on identification of novel therapeutic targets
• Primary human tissues as well as pre-clinical model studies
• Studies focused on antibody-mediated injury in solid organ transplantation to identify or validate novel therapies
• Computational integration and analyses of relevant datasets to identify, characterize and validate novel targets, generate hypotheses and in silico models for new therapies in solid organ transplantation
• Novel computational approaches for drug repurposing and in silico identification and modelling of mechanisms of action of novel therapies in the field of solid organ transplantation.

Dr. Igor Jurisica is co-founder and CSO of LumiNet Bio Incorporated, which is involved in improving insights from multi-omics data. The other topic editors declare no competing interests with regard to the topic theme.

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Frontiers in Immunology

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