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Scientists discover proteins that could predict liver transplant rejection

Northwestern University researchers have discovered families of proteins that could potentially predict which patients may reject a new organ transplant.

A protein map

Human biology and proteins are tightly linked. The use of mass spectrometry-based proteomics has identified strong links between phenotypes and protein-level biology. There have been several efforts to map the composition of proteins, including two drafts of the human proteome in 2014, the Human Protein Atlas and the Human Blood Atlas. Unfortunately, these datasets do not precisely determine alternatively spliced sequences or post-translational modifications.

Measuring proteoforms (protein molecules) can capture the complete composition of proteins and refine phenotypic correlations. A reference map could also be used for next-generation technologies, such as single-cell proteomics.

The Blood Proteoform Atlas

In a recent study, published in Science, researchers further explored the primary structures of ~30,000 unique proteoforms expressed from 1,690 human genes across 21 cell types and plasma from human blood and bone marrow. The result, the Blood Proteoform Atlas, compiles nearly 10 times more unique proteoforms than previous studies. The team reported that these proteoforms better describe protein-level biology and are more specific indicators of differentiation compared to their corresponding proteins.

Th team explored the clinical application of this map by applying it within the context of liver transplantation. They examined which proteoforms appeared to become activated in response to the transplant and identified those that changed compared to patients who didn’t experience rejection. They then developed a panel of 24 proteoforms from this initial study and looked at them in other transplant recipient samples. Here, they found that the same proteoforms lit up as in the first study.

Co-corresponding author, Josh Levitsky, said:

“The promise here is to be able to use this panel moving forward to be able to identify patients who have no signs of rejection versus those who have very early evidence of rejection.

If we can pick up on this several weeks before rejection actually happens, we might be able to modify immunosuppression.”

The team will continue to examine how proteoforms change in transplant recipients over time in order to develop additional biomarkers that may help inform how they are treated down the line.

Image credit: canva

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Protein / Transplant