Increased Levels of the Bullous Pemphigoid BP180 Autoantibody Are Associated with More Severe Dementia in Alzheimer’s Disease

Kokkonen, Nina; Herukka, Sanna‐Kaisa; Huilaja, Laura; Kokki, Merja; Koivisto, Anne M.; Hartikainen, Päivi; Remes, Anne M.; Tasanen, Kaisa

doi:10.1016/j.jid.2016.09.010

Cited by 73 publications

(98 citation statements)

References 41 publications

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“…Here, we present two cases of elderly patients with BP230‐type BP who had dementia at the onset of BP. A previous study reported that 18% of patients with dementia have IgG autoantibodies to BP180; however, it is unclear whether the production of IgG autoantibodies to BP230 correlates with dementia . Notably, none of our cases showed oedematous erythema that is usually seen in typical BP.…”

contrasting

confidence: 52%

A possible association between BP230-type bullous pemphigoid and dementia: a report of two cases in elderly patients

et al. 2018

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contrasting

confidence: 52%

A possible association between BP230-type bullous pemphigoid and dementia: a report of two cases in elderly patients

et al. 2018

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“…A recent study revealed that in a group of patients with Alzheimer’s disease but no bullous pemphigoid, their sera contained much higher level of BP180 autoantibody than neurologically healthy controls. Furthermore, increased levels of the autoantibody were associated with more severe dementia [19]. Thus, it remains unclear whether neurological disease itself could increase the mortality risk, or the increased risk is conferred by functional impairment and decreased autonomy resulting from neurological disease.…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors for mortality in patients with bullous pemphigoid: a meta-analysis

Liu

Wang

et al. 2017

Arch Dermatol Res

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Bullous pemphigoid (BP) is a chronic debilitating autoimmune blistering disease that frequently occurs in the elderly population. Previous studies have suggested a high morbidity and mortality associated with BP. However, relatively few studies have investigated prognostic factors of BP mortality, and they showed considerably various results. This meta-analysis aimed to quantitatively assess the association between several potential prognostic factors and risk of mortality in bullous pemphigoid. A comprehensive search was performed using Pubmed, Embase, and Cochrane Library. Cohort studies that assessed prognostic factors of BP mortality were included. Random-effects model was utilized to calculate the pooled hazard ratio (HR). Publication bias was evaluated qualitatively by constructing a funnel plot and quantitatively by conducting Egger’s test. 14 studies were included comprising 2499 patients. Combined HRs suggested that advanced age (HR 1.63, 95% CI 1.34–1.97), presence of circulating antibodies (HR 1.77, 95% CI 1.20–2.62), concomitant dementia (HR 2.01, 95% CI 1.22–3.33), and concomitant stroke (HR 1.86, 95% CI 1.29–2.67) have an unfavorable impact on patient survival. Gender, disease extent, mucosal involvement, and indirect immunofluorescence result were not shown to be linked to mortality by our analysis. This study indicated that BP patients with older age, circulating antibodies, dementia, and stroke are at greater risk of mortality. Clinicians should be aware of this association and utilize this information in patient education and treatment process.Electronic supplementary materialThe online version of this article (doi:10.1007/s00403-017-1736-1) contains supplementary material, which is available to authorized users.

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“…Autoantibodies against the immunodominant NC16A domain of BP180 were found in 19% of Alzheimer's disease patients, but only 2% of controls had positive results. The levels of BP180 autoantibodies correlated with the level of cognitive decline 29 . Another factor behind the association between neurological and psychiatric disorders and BP could be the medication used for these diseases.…”

Section: Discussionmentioning

confidence: 92%

028 Psychiatric and neurological disorders are associated with bullous pemphigoid – nationwide Finnish Care Register study

Försti

Jokelainen

Ansakorpi

et al. 2016

Journal of Investigative Dermatology

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Bullous pemphigoid (BP) is an autoimmune blistering skin disease with increasing incidence. BP is associated with neurological disorders, but it has not been established, what subtypes of dementia and stroke are associated with BP, and what is the temporal relation between these diseases. Also, the association between BP and psychiatric disorders is controversial. We conducted a retrospective nationwide study, using the Finnish Care Register for Health Care diagnoses between 1987 and 2013. The study population of 4524 BP patients were compared with 66138 patients with basocellular carcinoma (BCC), neurological and psychiatric comorbid disorders were evaluated for both groups, and associations were estimated by Cox regression and logistic regression analyses. The strongest risk of developing BP was found after diagnosis of multiple sclerosis (MS) (OR=5.9, 95% CI 3.9-8.5). Among psychiatric diseases, the corresponding risk was strongest in schizophrenia (OR=2.7, 95% CI 2.0-3.5), and as a novel finding, also personality disorders (OR=2.2, 95% CI 1.3-3.3) preceded BP. In conclusion, many psychiatric disorders, especially schizophrenia, carry heightened risk for BP. Furthermore, several neurological diseases which cause central nervous system inflammation or degeneration were related to BP, and the association was strongest between MS and BP.Bullous pemphigoid (BP) is an autoimmune skin disease with incidence varying between 0.25 and 4.28/100.000 per year 1-3 . The age-adjusted incidence of BP has been reported to be on the rise 1-3 . BP typically presents with severe itching and blistering of the skin, but in up to 20% of patients blisters are completely absent and only excoriations or eczematous, urticated lesions are observed 4 . BP typically affects elderly people, has many comorbidities and carries an elevated risk of death compared with the general population of the same age [1][2][3][4] . The pathogenesis of BP is characterized by autoantibodies directed against the hemidesmosomal components between the basal keratinocytes of the epidermis and the extracellular matrix of the dermis, resulting in subepidermal blister formation. The main autoantigen is bullous pemphigoid antigen 180 (BP180, also known as BPAG 2 or collagen XVII), though BP patients may also have autoantibodies against bullous pemphigoid antigen 230 (BP230 or BPAG1), another hemidesmosomal protein 4 . Several studies have established an association between BP and neurological disorders, especially stroke, dementia and Parkinson's disease [5][6][7][8] . The mechanism behind this association has been suggested to be an autoinflammatory reaction against BP180 or the neuronal isoform of BP230 in the human brain 9,10 . However, previous studies did not specify the types of dementia or cerebrovascular stroke. Neurological disorders precede BP 5,6 , but it is unclear, whether the risk of developing neurological disorders is elevated after a diagnosis of BP.

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Increased Levels of the Bullous Pemphigoid BP180 Autoantibody Are Associated with More Severe Dementia in Alzheimer’s Disease

Cited by 73 publications

References 41 publications

A possible association between BP230-type bullous pemphigoid and dementia: a report of two cases in elderly patients

A possible association between BP230-type bullous pemphigoid and dementia: a report of two cases in elderly patients

Prognostic factors for mortality in patients with bullous pemphigoid: a meta-analysis

028 Psychiatric and neurological disorders are associated with bullous pemphigoid – nationwide Finnish Care Register study

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