Sera of Elderly Bullous Pemphigoid Patients with Associated Neurological Diseases Recognize Bullous Pemphigoid Antigens in the Human Brain

Abstract

Background: Bullous pemphigoid (BP) is an acquired autoimmune dermatosis that is often associated with various neurological diseases (ND) in the elderly. Previously, we reported that BP antigen 1 (BPAG1) of the mouse brain can be recognized by serum samples of BP patients with ND (BP+ND), indicating the possibility that BPAG1 could act as a shared autoantigen of the skin and brain. However, it is not known whether the serum of BP+ND patients could recognize BPAG1 in the human brain. Objectives: The aim of this study is to determine whether sera of BP+ND patients could recognize BP antigens in human brain tissue. Methods: Serum samples of BP+ND patients and those of age- and sex-matched BP patients without ND, ND patients without BP, and normal controls were obtained. Serum samples were examined by immunoblotting against protein extracts of human skin and brain. Results: A 230-kDa protein of human epidermal extract was recognized by 16 of 22 (72.7%) serum samples of elderly BP+ND patients, whereas it was recognized by 50, 0, and 0% of serum samples of BP, ND, and controls, respectively. A 230-kDa protein of human brain extract was recognized by 12 of 22 (54.5%) serum samples of BP+ND patients, whereas it was recognized by 9.1, 9.1, and 4.5% of serum samples of BP, ND, and controls, respectively. A 180- and a 165-kDa protein could also be recognized by a proportion of serum samples of BP and BP+ND patients. Conclusion: This study demonstrated that both human skin and brain contain immunogenic BPAG1 in BP+ND patients. We speculate that alterations of the central nervous system in the course of pathological changes of elderly ND patients could expose the neural isoforms of BPAG1 or other BP antigens. Autoantibodies against these antigens in the brain may cross-react with antigen in the skin, which may underlie the pathological development of BP.

A population-based study of the association between bullous pemphigoid and neurologic disorders

“…The skin and neurons are both derived from the ectoderm, and the same hemidesmosomal protein antigens involved in the pathogenesis of BP are also expressed in human neurons (9,10). With regard to BP antigen 1 (BP230), a majority (54.5%) of serum samples from patients with BP and neurologic disease recognized a 230-kDa protein of human brain extract (31). Another study also showed that both human skin and brain contain immunogenic BP230 in patients with neurologic disease and BP (32).…”

Mortality Rate in Bullous Pemphigoid: A Retrospective Monocentric Cohort Study

“…Another study recently found that patients with BP showed a 3.62-fold increased risk for neurological disease prior to the diagnosis of BP [33]. These observations are particularly intriguing since evidence has been provided indicating that BP180 and BP230 are expressed in the central nervous system [34,35,36] and mice with defects in the dystonin gene, encoding for various isoforms of BPAG1 (including the epithelial isoform BP230/BPAG1-e), develop dystonia and sensory nerve degeneration [33,37]. …”

Autoantibodies to Collagen XVII Are Present in Parkinson’s Disease and Localize to Tyrosine-Hydroxylase Positive Neurons

“…Epidemiologic studies indicate that neurologic disease is an independent risk factor for BP (Bastuji-Garin et al, 2011; Langan et al, 2011; Stinco et al, 2005). BP is most strongly associated with dementia and Parkinson’s disease (PD), where the incidence is 2–4 times the expected rates in these diseases (Chen et al, 2011; Taghipour et al, 2010; Yang et al, 2011). …”