牛皮癣皮肤中模拟棒状杆菌的高丰度表明了牛皮癣的病因。这一假设在一项探索性研究中得到了检验,其中用热处理的C.simulans和牛皮癣血清来源的IgG的提取物进行的western印迹(WB)分析显示出单个16kDa-WB带。蛋白质组学分析显示核糖体蛋白为候选C.s-抗原。肽分析出乎意料地显示牛皮癣血清来源的IgG已经含有31个棒状杆菌ssp的免疫肽。,表明存在天然双特异性抗体(BsAb)。此外,肽酶分析给出了372个与病毒和噬菌体蛋白相似的DECOY肽,包括白喉棒状杆菌噬菌体,和白喉毒素相似.引人注目的是,对人类肽的肽分析揭示了主要银屑病自身抗原的64个表位,例如丝聚蛋白的间隔区,hornerin重复和其他。大多数鉴定的免疫肽代表潜在的阳离子内在无序抗菌肽(CIDAMP),在表皮内产生。这些可能与细菌无序的蛋白质区域形成复合物,代表含有不连续表位的嵌合抗原。此外,在128个低丰度免疫肽中,48是假定的牛皮癣相关的,例如PGE2-的表位肽,维生素D3-和IL-10受体。Further,来自肿瘤抗原的47个免疫肽,和内源性逆转录病毒HERV-K。我认为持续感染产毒C.simulans会引发牛皮癣,CIDAMPs作为自身抗原加剧了自身免疫性疾病。天然BsAb的发现允许从微生物中鉴定抗原表位,病毒,自身抗原和肿瘤抗原,并且可能有助于开发具有抗原特异性调节性T细胞的表位特异性肽疫苗和治疗方法,从而以自身免疫性疾病特异性方式改善免疫耐受。
The high abundance of Corynebacterium simulans in psoriasis skin suggests a contribution to the psoriasis aetiology. This hypothesis was tested in an exploratory study, where western blot (WB) analyses with extracts of heat-treated C. simulans and psoriasis serum-derived IgG exhibited a single 16 kDa-WB-band. Proteomic analyses revealed ribosomal proteins as candidate C. s.-antigens. A peptidomic analysis unexpectedly showed that psoriasis serum-derived IgG already contained 31 immunopeptides of Corynebacteria ssp., suggesting the presence of natural bispecific antibodies (BsAbs). Moreover, peptidomic analyses gave 372 DECOY-peptides with similarity to virus- and phage proteins, including Corynebacterium diphtheriae phage, and similarity to diphtheria toxin. Strikingly, a peptidomic analysis for human peptides revealed 64 epitopes of major psoriasis autoantigens such as the spacer region of filaggrin, hornerin repeats and others. Most identified immunopeptides represent potential cationic intrinsically disordered antimicrobial peptides (CIDAMPs), which are generated within the epidermis. These may form complexes with bacterial disordered protein regions, representing chimeric antigens containing discontinuous epitopes. In addition, among 128 low-abundance immunopeptides, 48 are putatively psoriasis-relevant such as epitope peptides of PGE2-, vitamin D3- and IL-10-receptors. Further, 47 immunopeptides originated from tumour antigens, and the endogenous retrovirus HERV-K. I propose that persistent infection with a toxigenic C. simulans initiates psoriasis, which is exacerbated as an autoimmune disease by CIDAMPs as autoantigens. The discovery of natural BsAbs allows the identification of antigen epitopes from microbes, viruses, autoantigens and tumour-antigens, and may help to develop epitope-specific peptide-vaccines and therapeutic approaches with antigen-specific regulatory T cells to improve immune tolerance in an autoimmune disease-specific-manner.