New Evidence that Chronic Ulcerative Stomatitis is an Autoimmune Disease.
In the first study investigating the origins of a little-known condition called chronic ulcerative stomatitis (CUS), researchers at Tufts University School of Dental Medicine provide evidence that an autoimmune response contributes to the painful oral sores that characterize the disease. The study findings support the classification of CUS as a new autoimmune disease.
Chronic ulcerative stomatitis is characterized by painful, recurring sores in the mouth. Thus far, it has been diagnosed most frequently in white women in their 40's and 50's and may appear similar to oral erosive lichen planus. Only 39 cases of CUS have been reported in the English-language medical literature since it was identified as a clinically distinct condition in 1989, but it is likely under-diagnosed because of low awareness among clinicians and the extensiveness of the testing that would confirm its presence.
"Currently, diagnosing CUS requires a surgical biopsy which then must be sent to an outside lab for special processing for immuno-fluorescence microscopic examination. Accurate diagnosis is important because the usual treatment option for immunologically-mediated diseases, corticosteroids, is often not effective in treating CUS," said senior author, Lynn Solomon, DDS, MS, associate professor in the department of oral and maxillofacial pathology at Tufts University School of Dental Medicine (TUSDM).
"In previous studies, we identified that CUS patients had specific auto-antibodies - antibodies produced by an immune response to the body's own tissue - but we weren't sure whether these auto-antibodies were contributing to CUS or part of a benign biological process. In this study, we determined that auto-antibodies fulfill the criteria of pathogenetic antibodies and do contribute to the disease," she continued.
In this in vitro study, the researchers applied antibodies from four CUS patients to Human Skin Equivalents (HSEs), a three-dimensional model of skin tissues. At low concentrations, the CUS antibodies appeared to have no effect. At higher concentrations, however, the researchers reported complete detachment of the surface layer of tissue, known as epithelium.
The researchers found that the CUS auto-antibodies do not cause damage to the surface epithelial cells, but cause a change in the cell-binding proteins that allow the surface layer to attach to the connective tissue beneath them. This weakened cohesion results in breakdown of the tissue, which would result in the sores that characterize CUS.
"In our future research, we would like to gain a better understanding of the mechanisms linking the autoimmune response to ulcerative sores so that we can optimize approaches to managing the condition. Additional data will help us evaluate hydroxychloroquine therapy, an antimalarial drug used off-label that provides relief in many cases, but which is not well-tolerated by some patients and which may have serious side effects," said Solomon.
The first author on the paper, Mark Carlson, Ph.D., now at Organogenesis, Inc., is an alumnus of the Training in Education and Critical Research Skills (TEACRS) program at Tufts, where he was a fellow in Jonathan Garlick's lab at TUSDM. TEACRS, funded by the National Institute of General Biomedical Sciences, part of the National Institutes of Health, is a program that fosters academic biomedical research and education leaders.
An additional author is Jonathan Garlick, DDS, Ph.D., professor in the oral and maxillofacial pathology department at Tufts University School of Dental Medicine and a member of the cell, molecular & developmental biology program faculty at the Sackler School of Biomedical Sciences at Tufts. Garlick is also the director of the Center for Integrated Tissue Engineering (CITE) at Tufts University School of Dental Medicine, which is dedicated to furthering the understanding of regenerative medicine through the investigation of three-dimensional tissue models.
Solomon has authored four studies on CUS since 2003. In March 2010, she was the lead author on a study examining the effectiveness of a simpler and less expensive diagnostic tool for CUS that is in development with colleagues from TUSDM, Tufts University School of Medicine, and Beutner Laboratories.
Carlson MW, Garlick JA, Solomon LW. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. "Chronic ulcerative stomatitis: Evidence of autoimmune pathogenesis" Published online April 4, 2011, doi: 10.1016/j.tripleo.2010.12.020
About Tufts University School of Dental Medicine - Founded in 1868, Tufts University School of Dental Medicine (TUSDM) is committed to leadership in education, patient care, research and community service. Students obtain an interdisciplinary education, integrated with medicine, with access to training in dental specialties. Clinics managed at TUSDM provide quality comprehensive care to more than 18,000 diverse individuals annually, including those requiring special needs. Nationally and internationally, the School promotes health and educational programs and researches new procedures, materials and technologies to improve oral health.
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