Anti-BP180 Autoantibodies Are Present in Stroke and Recognize Human Cutaneous BP180 and BP180-NC16A.

Yanan Wang,Li Li,Aimee S Payne,Yiman Wang,Hongzhong Jin,Di Wang,Bin Peng,Christoph M Hammers,Xuming Mao

doi:10.3389/fimmu.2019.00236

Abstract

Objective: Current evidence has revealed a significant association between bullous pemphigoid (BP) and neurological diseases (ND), including stroke, but the incidence of BP autoantibodies in patients with stroke has not previously been investigated. Our study aimed to assess BP antigen-specific antibodies in stroke patients.Design: One hundred patients with stroke and 100 matched healthy controls were randomly selected for measurement of anti-BP180/BP230 IgG autoantibodies by enzyme-linked immunosorbent assay (ELISA), salt-split indirect immunofluorescence (IIF), and immunoblotting against human cutaneous BP180 and BP180-NC16A.Results: Anti-BP180 autoantibodies were found in 14 (14.0%) patients with stroke and 5 (5.0%) of controls by ELISA (p < 0.05). Sera from 13 (13.0%) patients with stroke and 3 (3.0%) controls reacted with 180-kDa proteins from human epidermal extract (p < 0.05). 11 (11.0%) of stroke and 2 (2.0%) of control sera recognized the human recombinant full length BP180 and NC16A (p < 0.05). The anti-BP180-positive patients were significantly younger than the negative patients at the time of stroke (p < 0.001).Conclusion: Development of anti-BP180 autoantibodies occurs at a higher frequency after stroke, suggesting BP180 as a relatively common autoantigen after stroke and providing novel insights into BP pathogenesis in aging.

Highlights

Bullous pemphigoid (BP) is an autoimmune blistering skin disorder most commonly found in the elderly [1]
Sera from patients with stroke (n = 100) and healthy controls (n = 100) were collected to examine anti-BP180/BP230 IgG antibodies by Enzyme-Linked Immunosorbent Analysis (ELISA)
Sera from 11 (11.0%) patients with stroke and 2(2.0 %) healthy controls recognized both of the human recombinant full length BP180 (P = 0.018) (Figure 1B) and human recombinant non-collagenous 16A (NC16A) (P = 0.018) (Figure 1C)

Summary

Introduction

Bullous pemphigoid (BP) is an autoimmune blistering skin disorder most commonly found in the elderly [1] It is characterized by circulating and tissue-bound autoantibodies directed against two hemidesmosomal components: the transmembrane BP180 (collagen XVII, BPAG2) protein, and the plakin family protein BP230 (BPAG1). AntiBP180 IgG autoantibodies play a key role in blister formation and correlate with disease activity in BP, at the time of diagnosis and at disease flare [2, 5]. These autoantibodies mainly target immunodominant epitopes of BP180 localized in the extracellular non-collagenous 16A (NC16A) domain [2]. The majority of BP patients react with the intracellular antigen BP230, which is thought to result from a secondary immune reaction after tissue damage [6]

Methods

Results

Conclusion