采用免疫蛋白质组学方法鉴定抗 SNRPB 抗体，SNRPB 是与小核核糖核蛋白相关的 B 和 B' 蛋白。
Identification of Antibody Against SNRPB, Small Nuclear Ribonucleoprotein-Associated Proteins B and B', as an Autoantibody Marker in Crohn's Disease using an Immunoproteomics Approach.
机构信息
Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
出版信息
J Crohns Colitis. 2017 Jul 1;11(7):848-856. doi: 10.1093/ecco-jcc/jjx019.
BACKGROUND
Current non-invasive biomarkers for Crohn's disease are limited in their utility. Progress in identifying individual autoantigens and autoantibodies in Crohn's disease has been challenging due to limitations of available immunoassays.
AIMS
Our aim was to identify autoantibodies associated with Crohn's disease that may be useful in diagnosis and management using an innovative protein array technology, namely nucleic acid programmable protein arrays [NAPPA].
METHODS
Serum samples of 96 patients with established Crohn's disease and 96 healthy controls were included and evenly split into discovery and validation sets randomly. Autoantibodies of both IgG and IgA classes were profiled against ~1900 human proteins in the discovery set on NAPPA. Autoantibodies discovered to be Crohn's disease-specific were further validated in the independent validation set by enzyme-linked immunosorbent assay.
RESULTS
Overall, reactivity of IgG autoantibodies was stronger than that of IgA autoantibodies; however, IgA autoantibodies showed greater differential reactivity between cases and controls. Four IgA autoantibodies against SNRPB, PRPH, PTTG1 and SNAI1 were newly identified with sensitivities above 15% at 95% specificity, among which anti-SNRPB-IgA had the highest sensitivity of 24.0%. Autoantibodies associated with specific disease subtypes were also found.
CONCLUSIONS
As one of the first studies to use immunoproteomics for the identification of autoantibodies in Crohn's disease, our results support the utility of NAPPA in implementing future expanded studies with better coverage of the human proteome and microbial proteomes relevant to Crohn's disease and identifying antibody markers that may have clinical impact in diagnosis and management.
背景
目前用于克罗恩病的非侵入性生物标志物在其应用中存在局限性。由于现有免疫测定法的限制，在识别克罗恩病中的个体自身抗原和自身抗体方面取得进展具有挑战性。
目的
我们的目的是使用创新的蛋白质阵列技术，即核酸可编程蛋白质阵列 [NAPPA]，鉴定与克罗恩病相关的自身抗体，这些自身抗体可能对诊断和管理有用。
方法
纳入 96 例确诊克罗恩病患者和 96 例健康对照者的血清样本，并随机分为发现和验证组。在发现组中，使用 NAPPA 对约 1900 种人类蛋白质进行 IgG 和 IgA 类自身抗体的分析。在独立的验证组中，通过酶联免疫吸附试验进一步验证发现的对克罗恩病具有特异性的自身抗体。
结果
总体而言，IgG 自身抗体的反应性强于 IgA 自身抗体；然而，IgA 自身抗体在病例和对照组之间表现出更大的差异反应性。有 4 种针对 SNRPB、PRPH、PTTG1 和 SNAI1 的 IgA 自身抗体具有超过 15%的灵敏度和 95%的特异性，其中抗-SNRPB-IgA 的灵敏度最高，为 24.0%。还发现了与特定疾病亚型相关的自身抗体。
结论
作为首次使用免疫蛋白质组学鉴定克罗恩病自身抗体的研究之一，我们的结果支持 NAPPA 在实施未来的扩展研究中的应用，这些研究将更好地覆盖人类蛋白质组和与克罗恩病相关的微生物蛋白质组，并鉴定可能对诊断和管理具有临床影响的抗体标志物。
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