帕金森和多发性硬化

Research letter

Parkinson disease and multiple sclerosis are not associated with autoantibodies against structural proteins of the dermal –epidermal junction

DOI:10.1111/bjd.14538

D EAR

E DITOR ,Bullous pemphigoid (BP),the most frequent autoimmune blistering disease,is associated with autoantibod-ies against two proteins of the dermal –epidermal junction (DEJ),BP180(type XVII collagen)and BP230[BP antigen 1(BPAG1)].1Two peculiar clinical features of BP are the advanced age of patients,with a mean age of between 75and 80years at disease onset,and its association with neurological disease.1Neurological diseases can be diagnosed in 30–50%of patients with BP,including cognitive impairment,stroke,epilepsy,Parkinson disease (PD)and multiple sclerosis (MS),with odds ratios (ORs)of 2Á2,1Á8–3Á3,1Á7–4Á0,2Á16–3Á50and 10Á7,respectively.2–7In addition,patients with MS are more likely to develop BP (OR 6Á7).8These findings are par-ticularly intriguing as the cutaneous target antigens of BP –BP180and BP230–are also expressed in the central nervous system (CNS).BP180expression was found in the cerebellum of rats and in autopsy samples of various neuroanatomical regions of human brain.9,10Mice with mutations in the dys-tonin gene encoding for various isoforms of BPAG1,including

the epithelial isoform BP230,develop severe dystonia and sensory nerve degeneration.11While PD is thought to be a primary neurodegenerative disorder,inflammatory responses seem to be secondary.12,13MS is believed to be initially induced via a peripheral immune response,and further driven by immune reactions within the CNS with secondary neurode-

generation.14During the process of neurodegeneration the two BP autoantigens in the CNS may have been exposed to the immune system,leading to the break of tolerance and,subsequently,to the generation of anti-BP180and anti-BP230antibodies,and,finally,to BP.9,15

In the present study,according to this hypothesis,we expected to detect serum autoantibodies against BP180and BP230more frequently in patients with PD and MS compared with age-and sex-matched controls.Alternatively,or addition-ally,environmental factors that increase susceptibility to the development of neurological disorders might similarly change the risk of autoimmune blistering dermatoses.8

We compared three age-and sex-matched groups of patients with PD (n =75,cohort A1),other neurological diseases [n =75,cohort A2;detailed information is given in Table S1(see Supporting Information)]and healthy controls (n =75,cohort A3)(Table 1).All sera from cohort A were prospec-tively collected and matched for age and sex.Furthermore,prospectively collected sera from consecutive patients with PD at another academic site (L €u beck;n =50,cohort C),a cohort

Table 1Overview of serological results

©2016British Association of Dermatologists British Journal of Dermatology (2016)1