The Immunology Role Of Exosomes In Bullous Pemphigoid Associated With Neurological Disease

Background:Bullous pemphigoid(BP)is an acquired autoimmune dermatosis which is often reported in association with neurological diseases(ND),including dementia and cerebral stroke etc.Exosomes are nano-sized extracellular vesicles that can be secreted by kinds of cells.Studies have found that exosomes contain specific proteins and nucleic acids and they can target specific cells or tissues.Exosomes have become a potentially effective method for disease diagnosis and treatment.Exosomes have great prospects in the development of precision medicine.Exosomes will play an important role in the prevention,diagnosis,treatment of BP and the mechanism of BP associated with ND.Objective:To study the pathogenicity of exosomes in serum,plasma,blister fluid and urine and the immunological characteristics of the antibodies in exosomes.To reveal the relationship and pathogenesis between BP and ND with exosomes.Methods:We collected the serum,plasma,blister fluid and urine from 16 patients with BP(63-90 years old),of which including six patients combine with ND(including cerebrovascular disease and dementia),serum,plasma and urine from 10 elderly patients without immune related skin disease or ND(ages 65-81)as normal control in Peking Union Medical College Hospital.Exosomes were extracted and analysed by electron microscopy,Nanosight Tracking Analysis(NTA)and Western Blot(WB).Related proteins and microRNA in exosomes were detected by qPCR and WB.Results:A large number of microvesicles were found in all patients and control samples.NTA detected that most of the vesicles were with a diameter of about 50-150 nm,and a large number of vesicular structure materials were observed under electron microscope.WB detected the exosome marker CD9.These experiments confirmed the presence of exosomes in patients and control samples.The exosomes were extracted and lysed from these samples,qPCR showed that P-S396-tau,P-T181-tau,miR-141 and miR-214 were significantly increased in blister fluid,serum,plasma and urine of BP patients,especially BP+ND patients,compared with the control group,while A ? 1-42,miR-146b-5p and miR-193a-3p were significantly decreased in blister fluid,serum,plasma and urine of BP patients,especially BP+ND patients,compared with the control group.Conclusions:Exosomes can be detected in serum,plasma,blister fluid and urine.The carriers of BP-related antibodies and genes in exosomes play an important role in BP and BP combined with ND.Exosomes have the potential to become a non-invasive detection tool for BP,and also have important value in the prevention,diagnosis and treatment of BP and ND.