Generation of Terminal Complement Complexes in Psoriatic Lesional Skin

Abstract

The complement system is thought to play an important role in the recruitment of neutrophils within the epidermis. In the present study we examined whether or not complement activation in psoriatic lesional skin results in the deposition of terminal complement complexes within the epidermis by measuring levels of SC5b-9 in the plasma and horny tissues of psoriatic patients. The levels of SC5b-9 in psoriatic plasma were significantly higher than those of controls or those of patients with atopic dermatitis. However, when the levels of SC5b-9 in the psoriatic plasma were compared before and after successful treatment of psoriasis, a significant reduction was observed after treatment. Studies of total protein extracts from lesional skin showed that, while no SC5b-9 was detected in the noninflammatory horny tissues, there were high levels of SC5b-9 in lesional horny tissues of psoriasis. By immunofluroescence using a monoclonal antibody to the C5b-9 neoantigen, deposition of C5b-9 was observed only in the stratum corneum of psoriatic skin. Thus the results of the present study suggests that in psoriatic lesional skin, the complement system is activated and that this complement activation proceeds all the way to the terminal step, generating membrane attack complex.

Topical Application of Mesenchymal Stem Cell Exosomes Alleviates the Imiquimod Induced Psoriasis-Like Inflammation

“…In the early 1970s, highly chemotactic activated complement components C3a and C5a were found to be elevated in psoriatic plaque relative to non-psoriatic scale [52][53][54][55]. The terminal complement complex C5b-9 was also found to be present in psoriatic lesional plaques but not in non-psoriatic plaque tissues [56]. The chemotactic activated complement components have been shown to be responsible for neutrophil migration into the stratum corneum to form Munro microabscesses characteristic of psoriasis [52][53][54][55].…”

Humoral Autoimmune Responses to the Squamous Cell Carcinoma Antigen Protein Family in Psoriasis

“…Although these findings show that T-cell-mediated events are of key pathogenic importance, it was reported more than 30 years ago that there is more IgG bound in vivo in the upper epidermis and stratum corneum of psoriatic lesions than in a variety of other inflammatory and hyperker-atotic skin diseases (Jablonska et al, 1975). Reports also describe the presence of products of complement activation in the surface stratum corneum of plaques, including C5a/C5a des arg (Schro ¨der and Christophers, 1986) and C5-9/membrane attack complex (Takematsu and Tagami, 1992). These data suggest that antigen-antibody interactions, which provoke complement activation, are of pathogenic relevance in psoriasis.…”

More than skin deep: atherosclerosis as a systemic manifestation of psoriasis

“…Reduced numbers and activity of Treg cells and the apparently resulting hyperactivity of Th1/Th17 subsets are encountered in both psoriasis and atherosclerosis 53–55,61–69 . Innate immune mechanisms common to psoriasis and atherosclerosis include lesional complement activation 70–75 and toll‐like receptor‐mediated events leading to cytokine‐driven inflammation 76–78 . Other cells and biologically active molecules (including cytokines, chemokines, adipokines, adhesion and costimulatory molecules) that are implicated in the pathogenesis of both psoriasis and atherosclerosis are listed and referenced in Table 1.…”