Lymphocytes, cytokines and adhesion molecules in chronic graft versus host disease.
Aims-To determine which inflammatory and immune pathways are implicated in the development of chronic graft versus host disease (GvHD) and whether differences between these pathways are responsible for the different presentations of chronic GvHD.Methods-Biopsy specimens of diseased and normal skin were obtained from patients presenting with lichen planus-like and sclerodermatous type chronic GvHD. Expression of epidermal cytokines, adhesion molecules and lymphoid surface markers was analysed by means of immunohistochemistry. Apoptosis was detected using the in situ nick endlabelling method.Results-In both GvHD lesion types, CD8+ cells predominated in the epidermis, whereas CD4+ cells were the most prevalentin the dermis. Apoptotickeratinocytes were found in diseased skin only and Fas antibodies labelled a considerable number of keratinocytes. The epidermis in both types of lesions expressed interleukin (IL) 1alpha, tumour necrosis factor (TNF) alpha and intercellular adhesion molecule (ICAM)-1, but dermal vascular cell adhesion molecule (VCAM)-1 expression was restricted to specimens of lichen planus-like GvHD. IL1alpha and E-selectin were expressed in normal looking skin of 55% and 80%, respectively, of patients with lichen planus-like GvHD.Conclusion-The similarity between expression of epidermal cytokines and adhesion molecules (with the exception of VCAM-1) and lymphocyte phenotype in lichen planus-like and sclerodermatous GvHD strongly suggests that the latter occurs as a consequence of the healing process. VCAM-1 distinguishes between lichen planus-like and sclerodermatous lesions. IL1alpha and E-selectin are potential early markers of chronic GvHD.
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Service de Recherche en Hémato-Immunologie (DRM-DSV, CEA), Hôpital St Louis, Centre Hayem, 1 Avenue Claude Vellefaux, 75475 Paris, France.
Gluckman
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Le Goué
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Dubertret
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Carosella
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