Autoantibody profiling in multiple sclerosis using arrays of human protein fragments.
Autoantibody profiling in multiple sclerosis using arrays of human protein fragments.
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DOI：
10.1074/mcp.m112.026757
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发表时间：
2013-09
期刊：
影响因子：
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通讯作者：
Nilsson P
中科院分区：
文献类型：
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作者：
Ayoglu B;Häggmark A;Khademi M;Olsson T;Uhlén M;Schwenk JM;Nilsson P
用大量的抗原收集分析自身抗体谱系正在成为识别自身免疫性疾病的生物标记物的有力工具。在这里，我们采用了一种系统的、非直接的方法来筛选90名多发性硬化症相关诊断患者血浆中的免疫球蛋白。11,520个蛋白质片段(代表所有人类蛋白质编码基因的∼38%)的反应模式是在建立在人类蛋白质图谱中的平面蛋白质微阵列上产生的。在2,000多种抗原中观察到免疫球蛋白G反应，其中%仅见于单个个体。我们使用多发性硬化症亚组之间的反应性分布来选择384个抗原，然后在平面微阵列上重新评估，在更大的队列中(n=376)用悬浮珠阵列来证实，并在抑制试验中确认其特异性。在多发性硬化症亚型内部和之间的异质性模式中，发现51种抗原的识别频率不同，这些抗原富含转录调节蛋白。总之，使用蛋白质片段和互补的高通量蛋白质阵列平台促进了发现和验证潜在疾病相关自身免疫签名的另一种途径，这些签名现在被建议作为额外的抗原，用于跨多发性硬化症生物库的大规模验证研究。
Profiling the autoantibody repertoire with large antigen collections is emerging as a powerful tool for the identification of biomarkers for autoimmune diseases. Here, a systematic and undirected approach was taken to screen for profiles of IgG in human plasma from 90 individuals with multiple sclerosis related diagnoses. Reactivity pattern of 11,520 protein fragments (representing ∼38% of all human protein encoding genes) were generated on planar protein microarrays built within the Human Protein Atlas. For more than 2,000 antigens IgG reactivity was observed, among which 64% were found only in single individuals. We used reactivity distributions among multiple sclerosis subgroups to select 384 antigens, which were then re-evaluated on planar microarrays, corroborated with suspension bead arrays in a larger cohort (n = 376) and confirmed for specificity in inhibition assays. Among the heterogeneous pattern within and across multiple sclerosis subtypes, differences in recognition frequencies were found for 51 antigens, which were enriched for proteins of transcriptional regulation. In conclusion, using protein fragments and complementary high-throughput protein array platforms facilitated an alternative route to discovery and verification of potentially disease-associated autoimmunity signatures, that are now proposed as additional antigens for large-scale validation studies across multiple sclerosis biobanks.