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BP180 Autoantibodies Target Different Epitopes in Multiple Sclerosis or Alzheimer's Disease than in Bullous Pemphigoid

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Date
2019
Author(s)
Tuusa, Jussi
Lindgren, Outi
Tertsunen, Hanna-Mari
Nishie, Wataru
Kokkonen, Nina
Huilaja, Laura
Izumi, Kentaro
Herukka, Sanna-Kaisa
Miettunen, Jouko
Shimizu, Hiroshi
Remes, Anne M
Tasanen, Kaisa
Unique identifier
10.1016/j.jid.2018.09.010
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Citation
Tuusa, Jussi. Lindgren, Outi. Tertsunen, Hanna-Mari. Nishie, Wataru. Kokkonen, Nina. Huilaja, Laura. Izumi, Kentaro. Herukka, Sanna-Kaisa. Miettunen, Jouko. Shimizu, Hiroshi. Remes, Anne M. Tasanen, Kaisa. (2019). BP180 Autoantibodies Target Different Epitopes in Multiple Sclerosis or Alzheimer's Disease than in Bullous Pemphigoid.  Journal of investigative dermatology, 139 (2) , 293-299. 10.1016/j.jid.2018.09.010.
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CC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
Abstract

Neurologic patients have an increased risk for bullous pemphigoid (BP), in which autoantibodies target BP180, a cutaneous basement membrane protein also expressed in the brain. Here we show that 53.6% of sera from patients with multiple sclerosis (MS) (n = 56) had IgG reactivity against full-length BP180 in immunoblotting, while in BP180 non-collagenous 16A ELISA (n = 143), only 7.7% of MS samples studied were positive. Epitope mapping with 13 fusion proteins covering the entire BP180 polypeptide revealed that in MS and Alzheimer’s disease (AD) patients, IgG autoantibodies target regions located in the intracellular and mid-extracellular parts of BP180, but not the well-known BP epitopes located in the non-collagenous 16A domain and the distal part of extracellular domain. In indirect immunofluorescence analysis, 8.1% of MS sera recognized the cutaneous basement membrane and in full-length BP180 ELISA analysis, 7.5% MS and AD sera were positive, indicating that these autoantibodies rarely recognize BP180 in its native conformation. Thus, in MS and AD patients, BP180 autoantibodies have a different epitope profile than in patients with BP, and seldom bind to native BP180. This explains the inability of these autoantibodies to cause skin symptoms. Our results suggest that the autoantibodies against BP180 alone are not sufficient to induce BP in MS and AD patients.

Subjects
AA   amino acid   AD   Alzheimer’s disease   BP   bullous pemphigoid   FP   fusion protein   MS   multiple sclerosis   NC16A   non-collagenous 16A   
URI
https://erepo.uef.fi/handle/123456789/7501
Link to the original item
http://dx.doi.org/10.1016/j.jid.2018.09.010
Publisher
Elsevier BV
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  • Terveystieteiden tiedekunta [1324]
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