Bullous pemphigoid antigen 1 isoforms: potential new target autoantigens in multiple sclerosis?

Laffitte, Emmanuel; Burkhard, Pierre; Fontao, Lionel; Jaunin, Fabienne; Saurat, Jean‐Hilaire; Chofflon, Michel; Borradori, Luca

doi:10.1111/j.1365-2133.2004.06338.x

Cited by 56 publications

(49 citation statements)

References 23 publications

(30 reference statements)

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“…Conceivably, an autoimmune response initially directed against a neuronal isoform of BPAG1 (BPAG1-n) encoded by the dystonin gene may secondarily trigger an autoimmune response against the epithelial isoform of BPAG1, according to the ''epitope spreading'' phenomenon (Fairley et al, 2004). The two isoforms share the same sequence in their terminal portion, which is recognized by anti-BPAG1 antibodies from BP patients (Laffitte et al, 2005). Recombinant BPAG1 fragments have been identified in cerebrospinal fluid from patients with multiple sclerosis (Laffitte et al, 2005), and serum from BP patients with neurological diseases recognized BPAG1 in mouse skin and brain extracts (Li et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Bullous Pemphigoid in the Elderly: A Prospective Case–Control Study

Bastuji‐Garin¹,

Joly²,

Lemordant³

et al. 2011

Journal of Investigative Dermatology

260

281

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A rise in the incidence of bullous pemphigoid (BP) was documented recently in Europe, and the main risk factors for BP remain unknown. We conducted a multicenter case-control study to evaluate risk factors for BP. We identified 201 incident BP cases and 345 controls individually matched for age, gender, center, and place of residence (home, nursing home, or extended-care facility). We used univariate and multivariate logistic regression analyses to compare drugs used for over 3 months, comorbidities, and physical and cognitive impairments between cases and controls. Mean age of BP patients was 84.2 (±8.7) years. Factors independently associated with BP by multivariate analysis were major cognitive impairment (odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.24-3.87), bedridden condition (OR, 2.19; 95% CI, 1.23-3.89), Parkinson's disease (OR, 2.16; 95% CI, 1.09-4.27), unipolar or bipolar disorder (OR, 5.25; 95% CI, 1.21-22.86), and chronic use of spironolactone (OR, 2.30; 95% CI, 1.20-4.46) or phenothiazines with aliphatic side chains (OR, 3.70; 95% CI, 1.21-11.34). Chronic analgesic use was associated with a lower risk of BP (OR, 0.49; 95% CI, 0.30-0.81). Thus, risk factors for BP include neurological disorders, particularly dementia and Parkinson's disease, psychiatric disorders (unipolar and bipolar disorders), bedridden condition, and chronic use of several drugs.

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Section: Discussionmentioning

confidence: 99%

Risk Factors for Bullous Pemphigoid in the Elderly: A Prospective Case–Control Study

Bastuji‐Garin¹,

Joly²,

Lemordant³

et al. 2011

Journal of Investigative Dermatology

260

281

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“…It has been suggested that accumulation of neurofilaments might induce a tolerance breakdown against the neuro-isoform of BPAG1, that could subsequently led to a cross reaction against the epidermal form of BPAG1 [9, 11, 13, 17]. However, this hypothesis has never been clearly demonstrated and the expression of the homologous part of the epidermal and neuronal isoform of BPAG1 in the human brain remains debated [17, 18]. Therefore, we were prompted to assess the prevalence of neurological disorders in a series of BP patients.…”

Section: Discussionmentioning

confidence: 99%

Neurological Disorders in Patients with Bullous Pemphigoid

et al. 2007

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Background: Unexpected cases of bullous pemphigoid (BP) have been reported in adult patients with various neurological disorders suggesting a possible relationship between these diseases. Objectives: (1) To determine the prevalence and types of neurological disorders in patients with BP, (2) to assess patients’ functional impairment, and (3) to compare the clinical and biological findings as well as prognosis of BP patients presenting with or without neurological disorders. Methods: BP patients with neurological disorders were selected in a series of 341 consecutive BP patients treated in 20 French Dermatology Departments. Functional impairment was prospectively assessed using the Karnofsky score which is a measure of patients’ general condition. Results: At least one neurological disorder was present in 123 of the 341 BP patients (36%). They primarily consisted of dementia (n = 68; 20%; 95% CI: 16–25%), cerebral stroke (n = 52; 15%; 95% CI: 4–19%), and/or Parkinson’s disease or parkinsonism (n = 32; 9%; 95% CI: 7–13%). BP patients with neurological disease were older than patients without neurological disease (83.8 ± 7.5 years vs. 79.3 ± 10.3 years, p < 10^–4). They also had a lower Karnofsky score (47 ± 19% vs. 74 ± 20%, p < 10^–4). One-year overall survival rates of the two groups were 50.8% (95% CI: 41.8–59.7) and 78.7% (95% CI: 73.0–84.2), respectively (p < 10^–4). In contrast, the number of bullae and main biological features at baseline were not different between the two groups of patients. Conclusion: This study demonstrated a high frequency of neurological disorders, particularly dementia, in BP patients. Most of these patients had a severe functional impairment and a poor prognosis.

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“…El mecanismo patogénico de esta asociación se desconoce actualmente, aunque un trabajo apunta a que puede existir una reactividad cruzada entre las isoformas epitelial y neural de BPAG1 tras el acontecimiento neurológico. Esto daría lugar a la exposición al sistema inmunológico de la forma neural, lo que desencadenaría la respuesta con autoanticuerpos contra la isoforma epitelial y, consecuentemente, la enfermedad ampollosa 10 . Este fenómeno se ha postulado al demostrarse experimentalmente que el suero de pacientes con PA y enfermedad neurológica reaccionaba contra extractos de piel y cerebro de ratones 11 .…”

Section: Introductionunclassified

Asociación de penfigoide y enfermedad neurológica: estudio de casos y controles

Casas-de-la-Asunción

Ruano-Ruiz

Rodríguez-Martín

et al. 2014

Actas Dermo-Sifiliográficas

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Bullous pemphigoid antigen 1 isoforms: potential new target autoantigens in multiple sclerosis?

Abstract: These results raise the possibility that a subset of patients with MS develops an autoantibody response to the neuronal variants of BPAG1. These findings potentially open the avenue of neuronal BPAG1 variants being novel targets of autoantibodies in neurological diseases.

Cited by 56 publications

References 23 publications

Risk Factors for Bullous Pemphigoid in the Elderly: A Prospective Case–Control Study

Risk Factors for Bullous Pemphigoid in the Elderly: A Prospective Case–Control Study

Neurological Disorders in Patients with Bullous Pemphigoid

Asociación de penfigoide y enfermedad neurológica: estudio de casos y controles

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