The Role Of Bullous Pemphigoid Antigen 1 And 2 In Bullous Pemphigoid Accompanied By Neurological Diseases

Bullous pemphigoid (BP) is an acquired autoimmue blistering diseases. It mainly occurs in the elderly. Many epidemiological studies suggested a possible relationship between BP and various neurological diseases (ND). The most common NDs reported were dementia, cerebral stroke, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis etc. The pathogenic relationship between BP and neurological diseases is not clear. Immunological cross-reactions may play a role in the association of these two diseases. We analyzed the clinical data of 22 BP patients with ND. To investigate the role of BPAG1 and BPAG2 in BP accompanied by ND. We tested the reactivity of the sera obtained from 22 BP patients with ND (BP+ND group), age and sex matched controls include 22 BP patients without ND (BP group), 22 patients with ND (ND group) and 22 normal controls (N group). The sera were assayed by immunoblotting against the human epidermis extract, the mouse brain extract and the human brain extract.Part 1. Objectives To investigate the reactivity of the sera of the four groups of patients with BPAG1 and BPAG2 in mouse brain. Methods The sera of BP+ND group, BP group, ND group and N group were assayed by immunoblotting against the human epidermis extract and the mouse brain extract. Results Analysis of patient's clinical data revealed that the diagnoses of BP in all of these 22 BP+ND patients were at the age of 77.7±7.9 (60-97) years old. Whereas, the average age of onset of ND was at 72.0±7.3 (55-88). The onset of BP was after ND in all of these patients. The average interval between ND and BP was 5.7±2.6 (2-12) years. Both of the 230kDa protein and 180kDa proteins of human epidermis extract could be recognized by part of the collected serum samples. The positive rates of 230kDa protein in BP+ND group, BP group, ND group and N group were 72.73%,50%,0%,0%, respectively. The postive rate of 180kDa protein in the four groups were 63.6%,59.1%,13.6% and 4.5%. The 230kDa protein of mouse brain extract was recognized by 12 of 22 (54.5%) sera samples obtained from BP+ND group, and the positive rates of 230kDa protein in BP group, ND group and N group were 4.5%,9.1%,0%, respectively. The 180kDa protein of mouse brain extract was recognized by 13 of 22 (59.1%) sera samples obtained from BP+ND group, and the positive rates of 180kDa protein in BP group, ND group and N group were 18.2%,36.4%,9.1%, respectively. Conclusions Sera of patients of bullous pemphigoid associated with neurological diseases could recognize BPAG1 and BPAG2 in the mouse brain.Part 2. Objectives To investigate the reactivity of the sera of the four groups of patients with BPAG1 and BPAG2 in human brain. Methods The sera of BP+ND group, BP group, ND group and N group were assayed by immunoblotting against the human brain extract. Results A 230 kDa protein of human brain extract was recognized by 12 of 22 (54.5%) serum samples of BP+ND, whereas it was recognized by 9.1%,9.1% and 4.5% of serum samples of BP, ND, and N, respectively. A 180 kDa protein of human brain extract was recognized by 13 of 22 (59.1%) serum samples of BP+ND, whereas it was recognized by 18.2%,27.3% and 4.5% of serum samples of BP, ND, and N, respectively. Conclusions Sera of patients of bullous pemphigoid associated with neurological diseases could recognize BPAG1 and BPAG2 in the human brain. We speculate that alterations of the central nervous system in the course of neurological diseases of ND patients could expose the neural isoforms of BPAG1 and/or BPAG2. Cross reactions of these auto-antibodies with skin may underlie the pathological development of BP.