Immunohistopathological characterization and the impact of topical immunomodulatory therapy in oral chronic graft-versus-host disease: A pilot study.

Abstract

To characterize the immunohistopathological features of oral chronic graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells. Paired oral cGVHD biopsies obtained before (n=12) and 1month after treatment (n=12) with topical dexamethasone (n=8) or tacrolimus (n=4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c-kit, and FoxP3. Controls included acute GVHD (aGVHD; n=3), oral lichen planus (OLP; n=5), and normal tissues (n=5). Oral cGVHD specimens prior to treatment were mainly characterized by basal cell squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3+ , CD4+ , CD8+ , CD103+ , CD163+ , and FoxP3+ cells, which were higher than in normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD, and dexamethasone reduced the number of CD4+ and CD103+ cells. The high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral cGVHD is largely T-cell-driven with macrophage participation. The impact of topical immunomodulatory therapy was variable, reducing histological inflammatory features, but with a weak clinicopathological correlation. Topical dexamethasone reduced the expression of CD4 and CD103, which may offer novel therapeutic targets.