When a New Immune System Attacks
NIDCR scientist studies how graft-versus-host disease develops in the mouth
Growing up prone to cavities meant Jacqueline Mays, D.D.S., MHSc, Ph.D., was a regular at her family dentist as a kid.
During those visits Mays became fascinated by all the gadgets and impressed by how quickly the dentist could fix problems in the mouth. “As a child, it made me want to do something useful to help people,” she says.
Along with her interest in dentistry, Mays developed a passion for research while working in biomedical labs as a college student. She decided to pursue both disciplines, earning a DDS and PhD from the Ohio State University and completing her postdoctoral studies on influenza and immunology at NIH. In 2011, Mays joined NIDCR as a clinical research fellow, applying her expertise in clinical dentistry and immunology to understand immune responses in the mouth, which can have broad implications. Her ongoing studies may even offer insights into how the body responds to coronavirus infection.
As a clinician-scientist, Mays works with patients who have undergone bone marrow or blood stem cell transplants to treat conditions such as blood cancers and sickle cell disease. The transplants aim to reboot patients’ immune systems by replacing faulty blood-forming stem cells with healthy ones from donors. However, more than half of transplant recipients develop a condition known as chronic graft-versus-host disease (GVHD), where the new immune cells recognize the patients’ tissues as foreign and attack them. While chronic GVHD can occur in multiple organs, the salivary glands and mucous lining of the mouth are affected in 40% to 80% of cases.
“The big mystery for our laboratory is ‘Why is the mouth so frequently targeted by this disease?’” says Mays, who recently became the first dentist at NIH to earn tenure-track status as a Lasker Clinical Research Scholar. The NIH program supports a small number of exceptional, early-career clinician-scientists to promote their development to fully independent investigators.
Mays leads a clinical program at NIDCR to better understand how oral GVHD develops. Patients with the condition often have oral ulcers, lace-like oral lesions, difficulty opening their mouths, and salivary gland damage, which can cause dry mouth. These symptoms can make eating and oral care difficult and increase the risks of tooth decay and oral infection.
“Often, our patients face a new normal after transplant,” says Mays. “We help them adjust, give them the tools to take care of their mouths, and, in some cases, treat their chronic GVHD.”
Currently, healthcare providers rely heavily on steroids to alleviate GVHD symptoms, but long-term use can cause hormone imbalances and joint problems. One of Mays’ goals is to find more effective ways to treat the condition.
“If we can figure out what triggers the immune activation within the oral cavity, it might give us some clues as to how to prevent this type of immune response,” says Mays.
To solve this puzzle, Mays and her team collect oral tissue samples from patients before and after their transplants to characterize the immune-related changes that occur in oral GVHD. Understanding the immune pathways that initiate the disease could help Mays’ group identify diagnostic markers and drug targets.
Recently, the team found that oral chronic GVHD patients had reduced levels of a protein in the saliva called ZG16B (zymogen granule protein 16 homolog B), raising the possibility that it and other saliva proteins could be used as non-invasive markers for diagnosis.
Mays’ research could also shed light on the origins of GVHD in other tissues, such as the lungs, intestines, and skin, which are biologically similar to the mouth. Lately, Mays is applying her expertise in mucosal and skin immunity to solve one of the ongoing mysteries of the COVID-19 pandemic: “COVID toes.” Her team is working with collaborators at the University of Wisconsin-Madison who are studying young patients afflicted with the painful, red-purple skin lesions that resemble frostbite and often appear after mild or asymptomatic SARS-CoV-2 infection. By understanding which immune cells are at play, the researchers may gain insights into why these patients with “COVID toes” fare relatively well with the disease overall.
“Dental research has a lot to offer and tremendously benefits the world of biomedical research,” adds Mays. “I am the first dentist to come through the Lasker program, but I won’t be the last.”
Related Links
References
Oral Complications of Chronic Graft-Versus-Host Disease. Fall-Dickson JM, Pavletic SZ, Mays JW, Schubert MM. J Natl Cancer Inst Monogr. 2019 Aug 1;2019(53):lgz007. doi: 10.1093/jncimonographs/lgz007. PMID: 31425593; PMCID: PMC6699578.
Clinical characteristics and cytokine biomarkers in patients with chronic graft-vs-host disease persisting seven or more years after diagnosis. Goklemez S, Im AP, Cao L, Pirsl F, Steinberg SM, Curtis LM, Mitchell SA, Cowen EW, Baruffaldi J, Rose J, Mays J, Ostojic A, Holtzman NG, Hakim FT, Pavletic SZ. Am J Hematol. 2020 Apr;95(4):387-394. doi: 10.1002/ajh.25717. Epub 2020 Jan 25. PMID: 31903638.
Salivary Zymogen Granule Protein 16B Drops at Onset of Chronic Graft-Versus-Host Disease: A Possible Salivary Biomarker for Oral Chronic Graft-Versus-Host Disease. Costa da Silva AC, Dodge J, Dhamala S, Do KT, Cho M, Rose JR, Hakim FT, Pavletic SZ, Mays JW. Biology of Blood and Marrow Transplantation Vol. 25, Issue 3S26 Published in issue: March 2019.
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October 2024