B cell survival holds key to chronic graft vs. host disease

(Press-News.org) Chapel Hill, NC – Leukemia and lymphoma patients who receive life-saving stem cell or bone marrow transplants often experience chronic side effects that significantly decrease quality of life, can last a lifetime, and ultimately affect their long-term survival.

In chronic Graft vs. Host Disease (GVHD), the differences between the donor bone marrow cells and the recipient's body often cause these immune cells to recognize the recipient's body tissues as foreign and the newly transplanted cells attack the transplant recipient's body. Symptoms can range from dry eyes and dry mouth, hair loss and skin rashes, vulnerability to infection, liver and lung and digestive tract disorders. For patients who received bone marrow or stem cells, it is estimated that 40-70 percent may experience chronic GVHD.

B cells, which produce proteins called antibodies, are one type of immune cell involved in GVHD. In a paper published in the journal, Blood, a team from the University of North Carolina's Lineberger Comprehensive Cancer Center, shows in the laboratory that B cells from patients with chronic GVHD are much more active than cells from patients without the disease. The team also outlines the cell signaling pathways that contribute to this increased activity – identifying a promising target for developing new therapies for the diseases. Jessica Allen, PhD, the paper's first author, says "We found that B cells from patients with active chronic GVHD were in a heightened metabolic state and resist programmed cell death."

Senior author, Stefanie Sarantopoulos, MD, PhD, assistant professor in the division of hematology/oncology and the departments of microbiology and immunology at the UNC School of Medicine, adds, "Steroids are currently our only standard treatment for chonic GVHD and they are often not effective. This study adds to our previously published work because it implicates the TNF family member protein called BAFF in the 'revved up' B-cell signaling we found in our patients. We hope to develop targeted therapeutic agents, like anti-BAFF agents or small molecule inhibitors of serine/ threonine kinases, for treatment of our chronic GVHD patients."

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Other UNC Lineberger researchers on the team include Albert Baldwin, PhD, Jonathan Serody, MD, Kristy Richards, MD, PhD, Thomas C. Shea, MD, Don A. Gabriel, MD, PhD, James Coghill, MD, Paul Armistead, MD, PhD, Matthew Fore, BA, and Jenna Wooten, PhD.

Additional team members from the UNC Stem Cell Transplant team and UNC Lineberger include Philip Roehrs, MD, Amber Essenmacher, Robert Irons, Allison Deal, Andrew Sharf, and Todd Hoffert.

Jerome Ritz MD, Corey Cutler, MD MPH, and Nazmim S. Bhuiya, BA, MPH from the Dana-Farber Cancer Institute also contributed to the research.

The study could not have been performed without the gracious consent of transplant patients at UNC and Dana Farber who donated extra blood samples. The University Cancer Research Fund (UCRF) and the UNC Tissue Procurement Core Facility supported collection of de-identified patient samples for these laboratory studies.

The research was funded by the National Marrow Donor Program through the Be The Match Foundation and National Institutes of Health grants K08HL107756 and CA142106.

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