Immunohistopathological characterization and the impact of topical immunomodulatory therapy in oral chronic GVHD: a pilot study

Abstract

Objective

To characterize the immunohistopathologic features of oral chronic graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells.

Material And Methods

Paired oral cGVHD biopsies obtained before (n=12) and one month 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).

Results

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.

Conclusion

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.

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