Immunohistochemical analysis of chronic discoid and subacute cutaneous lupus erythematosus—relation to immunopathological mechanisms

Abstract

An immunohistochemical analysis of skin biopsies was performed in 18 patients with cutaneous lupus erythematosus (LE), using the alkaline phosphatase and monoclonal anti-alkaline phosphatase method (APAAP). The study group was subdivided on the basis of clinical criteria into 10 patients with chronic discoid LE (CDLE) and eight patients with subacute cutaneous LE (SCLE). Using a panel of monoclonal antibodies the following results were obtained: (i) ICAM-1 was expressed on epidermal keratinocytes, dermal inflammatory cells, and endothelial cells in most biopsies, whereas LFA-1 was confined to the dermis. Attachments between keratinocytes or endothelial cells and activated T lymphocytes via ICAM-1/LFA-1 may be a possible mechanism of target/effector recognition in cutaneous LE. (ii) HLA-DR was expressed on epidermal keratinocytes and cells of the dermal infiltrate, but not on endothelial cells. HLA-DR+ cells probably function as antigen-presenting cells, leading to major histocompatibility complex-restricted cellular cytotoxicity in cutaneous LE. (iii) Interleukin 2 receptor expression on dermal inflammatory cells was weak, indicating non-specific activation of T lymphocytes. (iv) The dermal inflammatory cells were T lymphocytes, mainly of the helper/inducer subtype. B lymphocytes were rarely found in the dermis. In general, no significant immunohistochemical differences were found between CDLE and SCLE, suggesting that these variants represent clinical subtypes rather than different pathogenetic entities.

Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus

“…The differences in the pathogenic mechanisms that lead to cutaneous lesions rather than severe organ involvement are not yet completely understood; however, skininfiltrating activated lymphocytes are thought to play a crucial role in the induction and maintenance of this autoimmune disease (5,6,33).…”

“…Peripheral blood was obtained from patients with various subtypes of CLE (SCLE, DLE, LET) (n ϭ 12) as well as from normal healthy donors (n ϭ 18) and separated by Ficoll gradient centrifugation. The detection of Treg by analysis of CD4ϩ,CD25 high cells has produced conflicting results in patients with SLE (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)31,32). Therefore, we used a new intracellular staining method to directly visualize Foxp3ϩ Treg by flow cytometry, which was performed according to the manufacturer's protocol, as described previously (25).…”

“…However, it remains unclear which processes limit CLE to the skin in most patients. Putative autoaggressive CD3ϩ T cell infiltrates can be detected in the cutaneous lesions, whereas no overt systemic autoimmune T cell dysfunction has been described (5,6). Accordingly, CLE might be attributable to a subtle local alteration in tolerance rather than a systemic failure of peripheral tolerance mechanisms as in SLE.…”

Photoimmunology of Lupus Erythematosus and Dermatomyositis: A Speculative Review

“…The predominant cell type in this infiltrate is CD4' T-lymphocytes that express class I1 histocompatibility antigens (73,75,(85)(86)(87)(88)(89)(90)(91)(92)(93). Other markers of T cell activation including IL-2 receptor expression and radiolabeled thymidine incorporation are only variably seen o n these infiltrating T cells (75,88,89).…”

“…Class I1 histocompatibility antigens (74,75) and adhesion molecules involved in T cell binding interactions such as intercellular adhesion molecule (1CAM)-1 (75) can often be seen to be expressed by epidermal keratinocytes in cutaneous LE lesions. In preliminary studies, the "B7-3" costimulatory ligand that is expressed on antigen-presenting cells has been observed on keratinocytes of cutaneous LE lesions (personal communication, Dr. Jan Simon, December 1995).…”