Abstract
The practical implications of complement deposition in direct immunofluorescence (DIF) microscopy and its influence on the disease phenotype are poorly understood. We aimed to investigate whether the presence of complement deposition in DIF microscopy gives rise to differences in the morphological, immunological, and histological characteristics of patients with BP (bullous pemphigoid). We performed a retrospective study encompassing patients with BP in a specialized tertiary referral center. Logistic regression model was utilized to identify variables independently associated with complement deposition. The study included 233 patients with BP, of whom 196 (84.1%) demonstrated linear C3 deposition along the dermal-epidermal junction (DEJ) in DIF analysis. BP patients with C3 deposition had higher mean (SD) levels (645.2 (1418.5) vs. 172.5 (243.9) U/mL; p < 0.001) and seropositivity rate (86.3% vs.64.9%; p = 0.002) of anti-BP180 NC16A and less prevalent neutrophilic infiltrate in lesional skin specimens (29.8% vs. 52.4%; p = 0.041). C3 deposition was found positively associated with the detection of anti-BP180 NC16A autoantibodies (OR, 4.25; 95% CI, 1.38–13.05) and inversely associated with the presence of neutrophils in lesional skin (OR, 3.03; 95% CI, 1.09–8.33). To conclude, complement deposition influences the immunological and histological features of BP. These findings are in line with experimental data describing the pathogenic role of complement in BP.
Highlights
Bullous pemphigoid (BP) is a prototypical organ-specific subepidermal autoimmune bullous dermatosis, typified by autoantibodies targeting the hemidesmosomal proteins BP180 and/or BP230, which are expressed by basal keratinocytes abutting the epithelial dermal-epidermal junction (DEJ)
The diagnosis of BP was based on the following criteria: (i) suggestive clinical presentation; (ii) linear deposits of immunoreactants along the DEJ by DIF microscopy of a perilesional skin biopsy; (iii) detection of circulating autoantibodies binding to the epidermal side of 1 mL salt-split normal human skin by indirect immunofluorescence (IIF) microscopy and/or the presence of circulating IgG autoantibodies against BP180 NC16A and/or BP230, as identified by enzyme-linked immunosorbent assay (ELISA) [18,19]
The current study demonstrated that complement deposition occurred among 84.1% of patients withThBeP,cruerprreenstesnttuindgytdheemleoandsitnrgatiemdmthuantocroemacptalenmt iennDt dIFepmoiscirtoioscnoopcyc.uCrroemdpalmemoenngt8s4e.e1m%sotfopinafltiuenentsce wtihthe iBmPm, urnepolroegseicnatlinagndtheistloepaadtihnogloigmicmalufneaotrueraecstaonf tBPinasDpIaFtiemnitcsrwosicthopCy3. dCeopmospitlieomnepnrtesseenetmedswtoith inhfliugehnecreletvheelsimanmduhnigohloegridcaelteacntidonhirsattoepoafthBoPl1o8g0icNalCf1e6aAtuareustooafnBtiPboadsiepsaatisewntesllwaisthwiCth3 ldesespforseiqtiuoennt prneesuentrtoepdhwiliicthinhfiiglthraetreleinvelelssiaonndalhsikgihnebr idoeptseicetsi.onDeratetectoiofnBoPf1B80P1N8C0 1N6CA1a6uAtoaaunttoibanodtiibeosdaiseswaenldl atshe absence of neutrophils were found to be independently associated with complement deposition in multivariable analysis
Summary
Bullous pemphigoid (BP) is a prototypical organ-specific subepidermal autoimmune bullous dermatosis, typified by autoantibodies targeting the hemidesmosomal proteins BP180 and/or BP230, which are expressed by basal keratinocytes abutting the epithelial dermal-epidermal junction (DEJ). Of which C3 deposition is of high diagnostic significance, are typically observed in patients with BP and gestational pemphigoid [6]. Beyond the diagnostic importance of complement factors, it is thought that complement activation plays an important role in the pathogenesis of BP [7]. While early in the neonatal mouse model of BP activation of complement appeared as a prerequisite for blister induction by anti-BP180 IgG [8,9,10], subsequent in vitro experiments and studies in a humanized and an adult mouse model of BP challenged this conclusion by demonstrating complement-independent mechanisms of subepidermal blister formation [11,12,13,14,15]
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