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

Abstract

Background: 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. Objective: Our study aims to assess BP antigen-specific antibodies in stroke patients. Methods: 100 patients with stroke and 100 healthy controls were randomly selected to measure anti-BP180/230 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 cutis 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 in stroke (p<0.001). Limitations: Longitudinal changes in antibody titers and long-term clinical outcome for a long duration were not fully investigated. Conclusion: Development of anti-BP180 autoantibodies occur at a higher frequency after stroke, suggesting BP180 as a shared autoantigen in stroke with BP and providing novel insights into BP pathogenesis in aging.

Analysis of the autoimmune response against BP180 in patients with Alzheimer’s disease

“…In a systematic review, patients with BP had an increased risk of dementia [odds ratio (OR): 5.48 (95% CI: 3.26-9.23); P<0.001] and ND preceded BP in the majority of cases with a mean time interval of 6.7 years (18). According to our study and others, the development of BP autoantibodies against both the skin and neuronal forms of antigens in BP with ND might be related to cutaneous-and neuronalsubtype BP antigens that have different locations, epitopes, and natural conformations (19)(20)(21)(22). In this study, we randomly enrolled 48 patients with AD and 50 sex-and agematched healthy controls to detect the level of anti-BP180/ BP230 IgG autoantibodies in sera.…”

“…The recombination of human cutaneous full-length BP180 and BP180-NC16A and western blotting were performed as previously described (21). Briefly, primers were designed according to the full length BP180/NC16A cDNA sequence to amplify the target gene fragments by PCR and sequence for FLAG tag was incorporated into the cDNA.…”

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

“…We conclude that anti-BP180 autoantibodies could be detected at a higher rate in stroke patients than age- and sex- matched controls, supporting that BP180 could serve as a shared autoantigen in both stroke and BP. Our data suggest young age in stroke could be a risk factor for later developing BP and provide a molecular mechanism for BP associated with ND (23). The present study is limited by a relatively short follow-up time so that, although long enough to detect significant differences in serum reactivity, may not have been long enough to allow for the subsequent development of BP skin lesions.…”

“…The authors are grateful to Nan Yang, for her outstanding assistance. We also thank biorxiv (www.biorxiv.org) for publishing a pre-print of this manuscript (23).…”

Detection of underlying dementia in bullous pemphigoid patients using cognitive evaluation tests: a multicenter case-control study

“…It has been previously reported that several ND with inflammation or degeneration in the central nervous system were related to BP (5). Recently, we have shown that a significantly high level of BP antibodies could be detected in patients with stroke (6). Although the mechanism linking BP to ND is largely unclear, the current hypothesis is that damage of the brain tissue leads to exposure of BP antigen 1 (BPAG1 or BP230) and BP antigen 2 (BPAG2 or BP180) to the immune system and production of anti-BP180 antibodies that may cause blister formation at the basement membrane (7,8).…”