Langerhans Cells in Epidermodysplasia verruciformis

Abstract

T cell defect and anergy to contact sensitizers are characteristic of the depressed cell-mediated immunity in epidermodysplasia verruciformis (EV). In this disease the generalized infection with human papilloma viruses is associated with a high risk of skin cancers. Langerhans cell density was studied quantitatively in lesions and noninvolved epidermis of EV using OKT6 and anti-HLA-DR monoclonal antibodies with indirect immunofluorescence technique. No significant changes were found in apparently normal skin suggesting no primary defect of Langerhans cells in EV. A marked decrease in Langerhans cell number per unit of epidermal volume could be observed in EV lesions. This additional reduction of immunological surveillance at sites of potentially oncogenic human papilloma virus infection may contribute to the increased risk of malignant transformation in EV lesions.

Inverse modulation of intraepithelial Langerhans' cells and stromal macrophage/dendrocyte populations in human papillomavirus-associated squamous intraepithelial lesions of the cervix

“…The density of Langerhans' cells detected by anti-S100 antibody in the present study was similar to that previously reported with other antibodies, such as anti-CDla, in normal and pathological cervical tissues [51 ]. A similar depletion of Langerhans' cells has also been observed in HPV-related lesions of other squamous epithelia, even when these develop in the absence of any pre-existing metaplastic process, such as penile condylomata [51 ], cutaneous warts [19], laryngeal papillomas [18] and skin lesions of epidermodysplasia verruciformis patients [35], suggesting that HPV infection by itself is a main factor in the depletion of Langerhans' cells in SILs. It has been demonstrated that more than 90% of cervical SILs are HPV-associated [25,44,76] and that, with sufficiently sensitive diagnostic methods, HPV DNA can be detected in most preneoplastic cervical lesions.…”

Human Papillomavirus Type 8 Interferes with a Novel C/EBPβ-Mediated Mechanism of Keratinocyte CCL20 Chemokine Expression and Langerhans Cell Migration

“…Thus, Langerhans cells are key regulators of immune responses in skin bridging innate and adaptive immunity. Lesional areas of EV epidermis were found to be largely devoid of cells expressing MHC class II (HLA-DR) and CD1a, a marker of Langerhans cells [17]–[19]. It was hypothesized that this might contribute to HPV persistence in EV lesions.…”

Aspectos clínicos da epidermodisplasia verruciforme

“…A transformação maligna ocorre em torno de 30 a 50% dos casos e está associada aos HPVEVs oncogênicos, fatores genéticos do hospedeiro e à ação de co-carcinógenos extrínsecos, principalmente UVB e radioterapia. 1,5,8,12,28,31,32 Os doentes podem apresentar, precocemente, elastose solar e numerosas lesões de queratose actínica-símile nas áreas de maior fotoexposição. 8,28,33 Essas lesões immunosuppressor therapy) which can justify a generalized infection by HPV and cutaneous cancer (syndrome similar to EV).…”

“…The malignant transformation occurs in about 30 to 50% of cases and is associated with oncogenic HPVEVs, genetic factors of the host cell, and actions of the extrinsic co-carcinogens, mainly UVB and radiotherapy. 1,5,8,12,28,31,32 Patients can prematurely show solar elastosis and numerous actinic keratosis-like lesions in the areas of greatest photoexhibition. 8,28,33 These lesions demonstrate clinical characteristics equal to those observed population in general, but with more malignization power.…”