Joshua Levitsky, MD
Professor in Medicine-Gastroenterology and Hepatology and Surgery-Organ Transplantation
Organ Rejection Proteoforms
The Comprehensive Transplant Center is actively building a research infrastructure around four pillars – Immune Tolerance, Biomarker Discovery, Outcomes Research, and Engineered Tissues.
After a liver transplant, there’s only one way to confirm if the patient’s body is rejecting the new organ: clinicians have to sample the liver itself. The biopsy is not an inherently dangerous procedure, but a non-invasive method to monitor patients for signs of acute rejection could help physicians catch organ rejection early, giving them an opportunity to modify immune-suppression medication to prevent severe rejection and possible organ failure.
Conversely, non-invasive blood markers showing the absence of rejection could allow physicians to curtail immunosuppression more safely, reducing the side effects of those medications. This could help patient management and decision-making, and ultimately improve patients’ outcomes and quality of life after a liver transplant.
Analyzing immune cells from archived blood samples of liver transplant recipients, Kelleher and Levitsky found several proteoforms expressed at differential levels in patients who experienced acute rejection versus those who did not. Mostly operating through inflammatory signaling pathways, these proteoforms could be the biomarkers for which transplant physicians have been looking.
The findings, published in 2017 in the American Journal of Transplantation, set the stage for a recently awarded U01 grant from the National Institutes of Health. Levitsky, the principal investigator of the grant, will lead a multi-center study measuring proteoform markers of rejection and using these data to inform immune suppression treatment.
“This has never been done before in liver transplant patients,” said Levitsky who is a member of the Comprehensive Transplant Center. “This is a major opportunity for our transplant center to not only lead this area of translational research but also collaborate with transplant centers across the country.”
Toby TK, Abecassis M, Kim K, Thomas PM, Fellers RT, LeDuc RD, Kelleher NL, Demetris J, Levitsky J. Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers in Liver Transplant Recipients. Am J Transplant. 2017 Sep;17(9):2458-2467. doi: 10.1111/ajt.14359. Epub 2017 Jun 27. PMID: 28510335; PMCID: PMC5612406. Summary | Full Text
hhabra D, Alvarado A, Dalal P, Leventhal J, Wang C, Sustento-Reodica N, Najafian N, Skaro A, Levitsky J, Mas V, Gallon L “Impact of calcineurin-inhibitor conversion to mTOR inhibitor on renal allograft function in a prednisone-free regimen.” Am J Transplant, 2013, 13(11) p. 2902-11. Summary | Full Text (DOI)
Parikh ND, Levitsky J “Hepatotoxicity and drug interactions in liver transplant candidates and recipients.” Clin Liver Dis, 2013, 17(4) p. 737-47, x-xi. Summary | Full Text (DOI)
Levitsky J, Miller J, Huang X, Chandrasekaran D, Chen L, Mathew JM “Inhibitory effects of belatacept on allospecific regulatory T-cell generation in humans.” Transplantation, 2013, 96(8) p. 689-96. Summary | Full Text (PMC) | Full Text (DOI)
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