Increased Levels of the Bullous Pemphigoid BP180 Autoantibody Are Associated with More Severe Dementia in Alzheimer’s Disease Nina Kokkonen, Sanna-Kaisa.

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Increased Levels of the Bullous Pemphigoid BP180 Autoantibody Are Associated with More Severe Dementia in Alzheimer’s Disease Nina Kokkonen, Sanna-Kaisa Herukka, Laura Huilaja, Merja Kokki, Anne M. Koivisto, Päivi Hartikainen, Anne M. Remes, Kaisa Tasanen Journal of Investigative Dermatology Volume 137, Issue 1, Pages 71-76 (January 2017) DOI: 10.1016/j.jid.2016.09.010 Copyright © 2016 The Authors Terms and Conditions

Figure 1 BP180 and BP230 autoantibody values of control subjects and patients with Alzheimer’s disease. Sera from controls (circles) and patients with Alzheimer’s disease (AD) (squares) were tested for IgG reactivity against BP180 and BP230 using ELISA kits. BP180 ELISA assay was performed as duplicates for all samples. (a) Increased anti-BP180 values (cutoff value >9 U/ml, dashed line) were detected in 3 of 40 control samples and in 24 of 115 AD samples. The increased anti-BP180 values varied between 9.2 and 47.7 U/ml. Two control samples and four AD samples were excluded because they did not recognize full-length BP180 in immunoblotting. (b) Increased anti-BP230 values (cutoff value >9 U/ml, dashed line) were detected in 3 of 40 control samples and in 14 of 115 AD samples. The increased anti-BP230 values varied between 9.6 and 35.8 U/ml. BP, bullous pemphigoid. Journal of Investigative Dermatology 2017 137, 71-76DOI: (10.1016/j.jid.2016.09.010) Copyright © 2016 The Authors Terms and Conditions

Figure 2 Autoantibodies present in the sera of patients with Alzheimer’s disease detect BP180 in immunoblotting. Twenty-four Alzheimer’s disease (AD) samples and three control samples, all of which showed increased anti-BP180 levels in ELISA assay, were further analyzed by immunoblotting using human recombinant full-length BP180 expressed in COS-7 cells as a target antigen. Anti-human IgG was used as a secondary antibody. (a) Human polyclonal anti-BP180 (NC16A) antibody and sera taken from a patient with bullous pemphigoid (BP), a control patient, and a patient with AD all recognized a 180-kDa protein that was not detected in collagenase-treated cell extract. (b) Four examples of immunoblotting, which verified that anti-BP180 ELISA positive AD samples recognize the full-length BP180. The ELISA positive control sample did not recognize the full-length BP180. NC16A, noncollagenous 16A. Journal of Investigative Dermatology 2017 137, 71-76DOI: (10.1016/j.jid.2016.09.010) Copyright © 2016 The Authors Terms and Conditions