Immunohistological analysis of immune cells in blistering skin lesions

Abstract

Background: Bullous skin lesions are characterised by the presence of intraepidermal or subepidermal bullae. Although inflammatory cell infiltrate is a constant feature in these lesions, their immunophenotypic characterisation is still incomplete. Aim: To determine whether the development of bullous skin diseases is associated with changes in the inflammatory cell infiltrate. Materials and methods: 34 cases representing lesions with both intraepidermal and subepidermal bullae were examined using immunoperoxidase staining methods and antibodies targeting antigens for histiocytes (CD68), B cells (CD20+), T cells (CD3+), T cells with cytotoxic potential (T cell intracellular associated antigen, TIA1+) and activity (granzyme B, GRB+). The adjacent normal skin (lesions) and an additional five cases of normal skin were also examined (controls). Results: The transition from normal skin to lesional skin (lesions with intraepidermal and subepidermal bullae) was associated with a significant increase (p(0.05) in the density of total inflammatory cell infiltrate, CD68+ cells, CD3+ T lymphocytes, CD20+ B lymphocytes, TIA1+-resting cytotoxic T cells and GRB+ T cells with cytotoxic activity. Conclusions: The increase in inflammatory cell infiltrate during the transition from normal to lesional skin may reflect the presence of an increased antigenicity of the lesional cells or a response to some basement membrane components. CD68+ and CD3+ cells, especially the resting cytotoxic ones, achieved numerical dominance in these lesions. Cell-mediated immunity seems to have critical role in the development of these lesions.

Granzyme B is elevated in autoimmune blistering diseases and cleaves key anchoring proteins of the dermal-epidermal junction

“…GzmB is capable of cleaving cell receptors, cellular adhesion proteins, cytokines and important extracellular matrix (ECM) proteins, thus affecting tissue structure and function 6 – 8 . Of particular relevance to autoimmune skin blistering, GzmB accumulation at the DEJ has been reported by previous studies in bullous diseases and cutaneous adverse drug reactions 9 – 11 . However, with respect to mechanism of action in skin diseases, GzmB has been viewed almost exclusively in the context of CTL/NK-mediated keratinocyte apoptosis 12 – 15 while the recently recognized role of extracellular GzmB proteolysis 5 , 8 , 16 has not been considered.…”

“…GzmB accumulation at the DEJ is observed in bullous dermatoses such bullous pemphigoid 9 and dermatitis herpetiformis 10 , as well as in cutaneous adverse drug reactions including lichenoid drug eruption 49 , SJS/TEN and generalized bullous fixed drug eruption 11 . However, as the newly discovered, non-apoptotic roles for GzmB were not established at the time, none of the aforementioned studies considered extracellular GzmB-mediated proteolysis as a mechanism for DEJ disruption.…”

Correlation between IL-36α and IL-17 and Activity of the Disease in Selected Autoimmune Blistering Diseases

“…According to many studies, the blistering lesions change in time, with the occurrences from mild to severe influx. The reason of these changes is the cascade of inflammatory incidents that appear in sequence [ 25 ].…”

Immunophenotyping of inflammatory cells in subacute prurigo

“…Nevertheless, we observed an increased number of CD68+ cells in SP lesions. CD68 is a myelomonocytic marker identified in human dermal macrophages which also belongs to the group of antigen‐presenting cells participating in the initiation of the inflammatory process in various immune‐mediated conditions such as blistering skin diseases 9,17,18 . In a previous study on atopic dermatitis patients, there was an increase in macrophage numbers in acutely and chronically inflamed skin, whereas absolute dendritic cell numbers were unchanged, compared with non‐lesional atopic dermatitis skin 17 .…”