Epithelial class II antigen expression in cutaneous graft-versus-host disease

Area of Science:

• Immunology
• Transplantation Immunology
• Dermatology

Background:

• Class II histocompatibility antigens, such as human leukocyte antigen (HLA)-DR, are induced in target tissues during graft-versus-host disease (GVHD).
• The role of this induced expression in initiating the target tissue phase of GVHD, involving antigen presentation and immune cell recruitment, is not fully understood.

Purpose of the Study:

• To investigate whether induced HLA-DR expression is a necessary factor for the development of cutaneous GVHD in allogeneic bone marrow transplant recipients.

Main Methods:

• Analysis of 92 skin biopsies from 37 allogeneic bone marrow transplant recipients.
• Immunohistochemical staining for HLA-DR, Langerhans cells (OKT6), lymphocytes (CD4+, CD8+), and monocytes.
• Correlation of HLA-DR expression with GVHD onset, severity, cellular infiltrate composition, and immunosuppressive prophylaxis (cyclosporine vs. cyclophosphamide).

Main Results:

• Of 22 biopsies at GVHD onset, 12 showed no detectable HLA-DR (HLA-DR-), and 10 showed patchy-to-diffuse expression (HLA-DR+).
• HLA-DR- GVHD biopsies had predominantly CD8+ T cell infiltrates, while HLA-DR+ GVHD biopsies had mixed CD4+/CD8+ infiltrates and more monocytes.
• Cyclosporine prophylaxis was associated with HLA-DR- GVHD, whereas cyclophosphamide yielded mixed results.
• HLA-DR expression was not consistently required for the target phase of GVHD, with some patients developing GVHD without detectable HLA-DR.

Conclusions:

• Induced class II antigen (HLA-DR) expression is not essential for the development of the target phase of cutaneous GVHD in most patients studied.
• The composition of the cellular infiltrate differs between HLA-DR- and HLA-DR+ GVHD.
• Immunosuppressive regimens may influence HLA-DR expression patterns during GVHD.