Experimental acantholysis by complement-fixing intercellular antibodies

Abstract

Complement-fixing intercellular antibodies were detected in 10 of 17 sera from untreated pemphigus patients. The role of complement in the organ culture system was investigated using these sera. Ten sera possessing complement-fixing intercellular antibodies showed IgG binding to the intercellular substance in the organ-cultured skin and acantholysis-like changes were observed in eight cases. C3 deposition was not seen in any case. However, after treatment of the sections of cultured skin with fresh normal human serum, complement fixation of the intercellular substance by bound IgG was revealed in all the ten cases. No significant differences in the grade of acantholysis-like changes between the complement-depleted system and the complement-supplied system were observed. Complement does not appear to be necessary in the acantholytic process in the in vitro organ culture system, even though we considered the presence of complement-fixing intercellular antibodies.

Cutaneous Inflammation: Prototypes of Immunological Mechanisms Involving the Skin

“…It represents a type II adaptive hypersensitivity reaction where complement fixing IgG is directed against antigens on the skin hemidesmosome adhesion complex (BP180 or BP230) of the basement membrane (Liu et al 2017;Nishie Fig. 6 Distribution of desmogleins in normal skin and oral mucosa and the effects of their disruption in pemphigus vulgaris and pemphigus foliaceus by antibodies and complement activation; activated B-cells, via stimulation by IL-4 from Th2 T-cells, secrete complement fixing IgG that binds and disrupts these molecules resulting in intercellular discohesion (Hashimoto et al 1982) 2014) (Fig. 12).…”

Cutaneous Inflammation: Prototypes of Immunological Mechanisms Involving the Skin

“…Distribution of desmogleins in normal skin and oral mucosa and the effects of their disruption in pemphigus vulgaris and pemphigus foliaceus by antibodies and complement activation; activated B-cells, via stimulation by IL-4 from Th2 T-cells, secrete complement fixing IgG that binds and disrupts these molecules resulting in intercellular discohesion (Hashimoto et al 1982). While desmoglein-3 is concentrated in the lower keratinocyte layers, desmoglein-1 is concentrated in the most superficial layers.…”

The relevance of complement in pemphigoid diseases: A critical appraisal

“…Impaired complement system activation or regulation has been observed in many dermatological diseases, such as hereditary ( 12 ) and acquired angioedema ( 13 ), cutaneous small vessel ( 14 , 15 ) and hypocomplementemic urticarial vasculitis ( 16 ), SLE ( 17 , 18 ), psoriasis ( 19 , 20 ), acne vulgaris ( 21 , 22 ) and hidradenitis suppurativa ( 23 ). Moreover, the complement system is also involved in the pathogenesis of autoimmune blistering dermatoses (AIBD), in particular the pemphigoid group, including bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA), mucous membrane pemphigoid (MMP), pemphigoid gestationis (PG), and, to a lesser degree, the pemphigus group ( 24 – 28 ). C3 deposits along the dermal-epidermal junction (DEJ) are observed in approximately 90% of patients with pemphigoid diseases (PDs) ( 29 – 32 ).…”