IADR Abstract Archives
Dynamic Extracellular Matrix Changes in Oral Chronic Graft-versus-Host Disease
Objectives: Chronic graft-versus-host disease (cGvHD) is a major complication in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Resembling autoimmune-like diseases, cGvHD develops oral complications in around 70% of cases that can affect oral mucosa, salivary glands and result in reduced oral aperture. Oral mucosal symptoms include lichenoid-like features of hyperkeratinization, erythema and ulceration. Current treatments and diagnostics are limited due to a poor understanding of disease pathogenesis. We aimed to study changes in extracellular matrix (ECM) composition and turnover in relation to histopathological cGvHD severity. We hypothesized oral mucosal ECM provided a suitable niche to support tissue repair for cGvHD oral complications.
Methods: cGvHD and healthy oral mucosal biopsies were obtained from the Oral Medicine Clinic at Karolinska University Hospital (6months post-HSCT, n=27). Sections were graded for severity according to an in-house grading module (grades 0-3) based on presenting histopathological features. Immunohistochemical staining for collagens I and III, decorin and biglycan, and matrix metalloproteinases (MMPs) 1, 2, 9 and 12 was performed. The extent of immunostaining was quantified using image analysis software.
Results:
Dynamic changes in ECM composition were apparent with increasing severity, suggesting an early shift towards intraoral fibrosis with mild pathological cGvHD features. Collagen III and decorin localization dramatically reduced with severity (grade 3, p<0.0001) in parallel to an increase of collagen I (p<0.0001). MMP expression reflected the collagen turnover within tissues, with significant increases (p<0.0001) of MMPs 2, 9 and 12 between healthy (grade 0) and severe (grade 3). In comparison, MMP1 most strikingly increased between healthy and mild (grade 1, p<0.001).
Conclusions: Changes in ECM composition reflected dynamic wound healing processes in oral cGVHD. Although, the observed changes were not specific to oral cGvHD, the results suggest development of intraoral fibrosis with increasing severity. The study contributes to emerging knowledge on the pathogenesis of oral cGvHD.
Methods: cGvHD and healthy oral mucosal biopsies were obtained from the Oral Medicine Clinic at Karolinska University Hospital (6months post-HSCT, n=27). Sections were graded for severity according to an in-house grading module (grades 0-3) based on presenting histopathological features. Immunohistochemical staining for collagens I and III, decorin and biglycan, and matrix metalloproteinases (MMPs) 1, 2, 9 and 12 was performed. The extent of immunostaining was quantified using image analysis software.
Results:
Dynamic changes in ECM composition were apparent with increasing severity, suggesting an early shift towards intraoral fibrosis with mild pathological cGvHD features. Collagen III and decorin localization dramatically reduced with severity (grade 3, p<0.0001) in parallel to an increase of collagen I (p<0.0001). MMP expression reflected the collagen turnover within tissues, with significant increases (p<0.0001) of MMPs 2, 9 and 12 between healthy (grade 0) and severe (grade 3). In comparison, MMP1 most strikingly increased between healthy and mild (grade 1, p<0.001).
Conclusions: Changes in ECM composition reflected dynamic wound healing processes in oral cGVHD. Although, the observed changes were not specific to oral cGvHD, the results suggest development of intraoral fibrosis with increasing severity. The study contributes to emerging knowledge on the pathogenesis of oral cGvHD.