People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China, and University of Houston, Houston, Texas.
University of Houston, Houston, Texas.
Arthritis Rheumatol. 2019 Jun;71(6):941-951. doi: 10.1002/art.40830. Epub 2019 Apr 6.
The autoimmune etiology in psoriasis remains to be clarified. We therefore undertook this study to identify novel pathogenic autoantigens and autoantibodies in patients with psoriasis, with the aim of shedding light on the molecular and cellular basis of the pathogenesis of psoriasis and psoriatic arthritis (PsA).
In this study, we developed an autoantigen array system that harbors a variety of antigens, including typical autoantigens in rheumatic diseases as well as skin antigens, inflammatory mediators, and putative autoantigens in psoriasis. Serum samples from patients with psoriasis (n = 73) were used to interrogate the antigens on the array. In addition, enzyme-linked immunosorbent assays of individual autoantibodies were used in validation studies.
Levels of several autoantibodies were found to be elevated in the serum of patients with psoriasis compared to healthy controls; in particular, IgG autoantibodies against 2 novel antigens, LL-37 and ADAMTS-L5, were significantly increased in patients with psoriasis. Importantly, serum levels of IgG autoantibodies against LL-37 and ADAMTS-L5 were correlated with the Psoriasis Area and Severity Index, and reflected disease progression in longitudinally collected serum samples from patients with psoriasis. Importantly, both anti-ADAMTS-L5 and anti-LL-37 autoantibody levels were also significantly elevated in psoriasis patients with PsA compared to those without PsA, suggesting that these molecules may be involved in the pathogenesis of PsA.
Our findings indicate that these identified autoantibodies may be useful biomarkers and may serve as therapeutic targets in psoriasis and PsA.
银屑病的自身免疫病因仍有待阐明。因此，我们开展了这项研究，旨在鉴定银屑病患者中新型致病自身抗原和自身抗体，以期阐明银屑病和银屑病关节炎（PsA）发病机制的分子和细胞基础。
在这项研究中，我们开发了一种自身抗原阵列系统，该系统包含多种抗原，包括风湿性疾病的典型自身抗原以及皮肤抗原、炎症介质和银屑病中的推定自身抗原。使用来自银屑病患者（n=73）的血清样本来检测阵列上的抗原。此外，还使用个别自身抗体的酶联免疫吸附测定法进行验证研究。
与健康对照组相比，发现银屑病患者血清中几种自身抗体的水平升高；特别是，针对 2 种新型抗原（LL-37 和 ADAMTS-L5）的 IgG 自身抗体在银屑病患者中显著增加。重要的是，抗 LL-37 和抗 ADAMTS-L5 IgG 自身抗体的血清水平与银屑病面积和严重程度指数相关，并反映了银屑病患者纵向采集的血清样本中的疾病进展。重要的是，与无 PsA 的银屑病患者相比，患有 PsA 的银屑病患者的抗 ADAMTS-L5 和抗 LL-37 自身抗体水平也显著升高，表明这些分子可能参与了 PsA 的发病机制。
我们的研究结果表明，这些鉴定出的自身抗体可能是有用的生物标志物，并可作为银屑病和 PsA 的治疗靶点。
