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

Oral Dis. 2018 May;24(4):580-590. doi: 10.1111/odi.12813. Epub 2018 Mar 13.

Abstract

Objective: To characterize the immunohistopathological 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 1 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.

Keywords: biomarkers; chronic graft-versus-host disease; oral mucosa; topical therapy.

MeSH terms

  • Administration, Topical
  • Adult
  • Aged
  • Antigens, CD / metabolism*
  • Dexamethasone / therapeutic use*
  • Female
  • Forkhead Transcription Factors / metabolism
  • Glucocorticoids / therapeutic use*
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Humans
  • Immunohistochemistry
  • Immunomodulation
  • Immunosuppressive Agents / therapeutic use*
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Mouth Diseases / drug therapy*
  • Mouth Diseases / immunology
  • Mouth Diseases / pathology
  • T-Lymphocytes / metabolism
  • Tacrolimus / therapeutic use*
  • Young Adult

Substances

  • Antigens, CD
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucocorticoids
  • Immunosuppressive Agents
  • Dexamethasone
  • Tacrolimus