University of Oulu

Jussi Tuusa, Outi Lindgren, Hanna-Mari Tertsunen, Wataru Nishie, Nina Kokkonen, Laura Huilaja, Kentaro Izumi, Sanna-Kaisa Herukka, Jouko Miettunen, Hiroshi Shimizu, Anne M. Remes, Kaisa Tasanen, BP180 Autoantibodies Target Different Epitopes in Multiple Sclerosis or Alzheimer’s Disease than in Bullous Pemphigoid, Journal of Investigative Dermatology, Volume 139, Issue 2, 2019, Pages 293-299, ISSN 0022-202X, https://doi.org/10.1016/j.jid.2018.09.010

BP180 autoantibodies target different epitopes in multiple sclerosis or Alzheimer’s disease than in bullous pemphigoid

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Author: Tuusa, Jussi1; Lindgren, Outi1,2; Tertsunen, Hanna-Mari3;
Organizations: 1Department of Dermatology, PEDEGO Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
2Department of Pathology, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
3Institute of Clinical Medicine–Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland
4Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
5Center for Life Course Health Research and Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
6Research Unit of Clinical Neuroscience, Department of Neurology and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2019061019864
Language: English
Published: Elsevier, 2019
Publish Date: 2019-10-10
Description:

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.

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Series: Journal of investigative dermatology
ISSN: 0022-202X
ISSN-E: 1523-1747
ISSN-L: 0022-202X
Volume: 139
Issue: 2
Pages: 293 - 299
DOI: 10.1016/j.jid.2018.09.010
OADOI: https://oadoi.org/10.1016/j.jid.2018.09.010
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: This study was supported by the Northern Finland Health Care Support Foundation to JT, the Sigrid Jusélius Foundation, Finland to KT and JT. the University of Oulu Graduate School to OL, the Oulu University Hospital to KT and JT, the Academy of Finland grant to NK and KT, and Kuopio University Hospital to AMR.
Copyright information: © 2018 The Authors. Published by Elsevier, Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/