Histo-pathophysiology of oral mucosa in patients with chronic graft versus host disease

Objectives: Graft-versus-host disease (GVHD), a major complication of allogeneic hematopoietic stem cell transplantation, is classified as acute (aGVHD) or chronic (cGVHD). cGVHD manifests as an autoimmune-like disease affecting multiple sites. The oral cavity is commonly involved in 45-83% of cases that present with a diverse spectrum of clinical features, such as mucosal lesions, salivary gland dysfunction and restricted mouth opening present. Histological presentation of oral mucosal tissues resembles other autoimmune diseases, with strong proinflammatory processes but knowledge of the pathophysiological features are not well defined. We aimed to characterize the histo-pathophysiology of clinically-graded cGvHD (mild-severe) from oral buccal mucosa and to examine the magnitude and location of infiltration related to the clinical scoring.
Methods: Oral mucosal biopsies from graded-cGvHD and healthy patients were stained for histology and a panel of inflammatory markers. Slides were digitalized and staining quantified.
Results: Histological changes, such as flattening of rete ridges, thickened basement membrane and increased number of clear cells correlated with increasing severity. A significant increase (p=>0.05) in inflammatory markers; CD4, CD8, CD68, CD19, CD20, CD5 and CD1a were observed with increasing clinical severity of cGvHD across all regions of the oral mucosa when compared to healthy tissue. Inflammation was concentrated to the papillary layer of the lamina propria.
Conclusions: We report on the dynamic pathophysiological changes within cGVHD oral mucosal affected tissues related to the clinical-severity of the disease. This study points to the need for large cohort screening of oral mucosa tissues that will aid in the formulation of better clinical diagnoses of oral cGVHD.