Complement and cutaneous autoimmune blistering diseases

Abstract

Cutaneous autoimmune blistering diseases are associated with tissue injury and fluid accumulation within the skin. The initial trigger for the organ-specific damage is autoantibodies targeting skin autoantigens, which are involved in cell-cell or cell-matrix adhesion in the skin. Pemphigus autoantibodies bind to desmosomal antigens and cause intraepidermal blisters, while pemphigoid autoantibodies interact with hemidesmosomal or hemidesmosome-associated antigens and lead to dermal-epidermal junction separation. Local complement activation is a common feature for these skin blistering diseases and some complement components are readily detected in the lesional skin and blister fluids. This review summarizes the current knowledge on the role the complement system in skin blister formation. Characterization of the pathogenically relevant complement cascade and relative contribution of different pathways into complement activation provides new insights of disease pathology and may help develop better therapeutic strategies for these potentially fatal cutaneous blistering disorders.

The role of Fc receptors and complement in autoimmunity

“…The pathogenicity of anti-BP180 antibodies was first confirmed in vivo by passively transferring them into neonatal mice [28]. Studies using this experimental model revealed that subepidermal blistering triggered by anti-BP180 IgG depends on complement (C3 and C5) activation, by both the CP, and to a lesser extent, the AP, leading to generation of C5a and its binding to C5aR, followed by mast cell degranulation and neutrophilic infiltration (reviewed in [29]). Further experiments have identified FcγRIII as the only crucial receptor for the pathogenicity of anti-BP180 IgG, although the role of FcγRI or FcγRIV could not be excluded or investigated at that time [30].…”

Imunofluorescência direta e indireta

“…It appears that there is no correlation between antibody titers and the extension or activity of the disease. 3,28,43 Epidermolisis bullosa acquisita/ Bullous systemic lupus erithematosus IIF: It shows circulating anti-BMZ IgG antibodies in 25-50% of the patients. There is no correlation between antibody titers and the extension or activity of the disease.…”

Expression of keratins, epidermal proteins and inflammatory cells in superficial pemphigus dogs

“…Specific markers of active T-cells and B-cells have been commonly characterised in humans with autoimmune blistering diseases (Sitaru & Zillikens, 2005). Furthermore, it is important to note that an association between epidermal-specific auto-antibodies and complement proteins has been described previously in human pemphigus (Lessey et al, 2008;Qian et al, 2011); a cross-reaction among IgE, IgM, and IgG4 anti-DSG-1 response has been reported in human PF patients (Qian et al, 2011). In contrast, IgM autoreactivity was not detected when canine PF serum was used against either DSG-1 or DSC-1 (Bizikova et al, 2014), and canine PF showed dominant IgG auto-antibody reactivity (Pérez et al, 2002: Olivry et al, 2009).…”