title: Increased Levels of the Bullous Pemphigoid BP180 Autoantibody Are Associated with More Severe Dementia in Alzheimer's Disease.
abstract: Bullous pemphigoid (BP) is a subepidermal blistering skin disease, which has shown a strong association with neurological diseases in epidemiological studies. The BP autoantigens BP180 and BP230 are expressed in the cutaneous basement membrane and the central nervous system. Using BP180 and BP230 ELISA assays and immunoblotting against BP180, we analyzed the IgG reactivity in the sera of 115 patients with Alzheimer's disease (AD) and 40 neurologically healthy controls. BP180 autoantibodies were found in 18% of patients with AD, whereas only 3% of controls had positive results (P = 0.019). BP230 values were higher and more often elevated in patients with AD than controls, but not significantly. None of the positive AD sera that recognized the full-length human BP180 in immunoblotting reacted with the cutaneous basement membrane in indirect immunofluorescence analysis. Moreover, a retrospective evaluation of the hospital records of the patients with AD revealed neither BP diagnosis nor BP-like symptoms. Interestingly, increased BP180-NC16A autoantibody values correlated with cognitive decline measured by mini-mental state examination scores, but not with the concentration of AD biomarkers in cerebrospinal fluid. Our findings further the understanding of the role of BP180 as a shared autoantigen in neurodermatological interactions and the association between BP and neurodegenerative diseases.
authors.affiliation: Department of Dermatology, PEDEGO Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Kokkonen
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Sanna-Kaisa
authors.initials: SK
authors.lastname: Herukka
authors.affiliation: Department of Dermatology, PEDEGO Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Huilaja
authors.affiliation: Department of Anesthesia and Operative Service, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Kokki
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Koivisto
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Hartikainen
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Remes
authors.affiliation: Department of Dermatology, PEDEGO Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: kaisa.tasanen@oulu.fi.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Tasanen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D024041:Non-Fibrillar Collagens / Q000097:blood*; D010391:Pemphigoid, Bullous / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D011379:Prognosis; D012720:Severity of Illness Index; D000097805:Collagen Type XVII
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII