Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays.
Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays.
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DOI：
10.1186/ar3800
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发表时间：
2012-04-17
影响因子：
4.9
通讯作者：
LaBaer J
中科院分区：
文献类型：
--
作者：
Gibson DS;Qiu J;Mendoza EA;Barker K;Rooney ME;LaBaer J
幼年特发性关节炎（JIA）是一种异质性疾病，其特征是儿童中不明原因的慢性关节炎症。 JIA 是一种自身免疫性疾病，据报道 JIA 患者体内存在少量自身抗体。抗体标记物的鉴定可以改善现有的患者临床管理。应用高通量平台核酸可编程蛋白阵列 (NAPPA) 进行了一项初步研究，以评估一小群幼年关节炎患者的体循环和滑膜关节中存在的抗体水平。对 10 名 JIA 患者的血浆和滑液进行了针对 NAPPA 上 768 种蛋白质的抗体筛查。 NAPPA 的定量重现性通过 > 0.95 的阵列内和阵列间相关性得到证明。在整个研究队列中，还观察到血浆和滑液之间的抗体水平存在很强的相关性（r = 0.96）。所有患者样本类型之间的 18 种抗体水平存在差异。通过无监督的层次聚类分析，将患者分为具有不同抗体特征的两种临床亚型。 NAPPA 提供了一个高通量定量可重复平台，可在显微镜载玻片上的蛋白质组水平上筛选疾病特异性自身抗体。循环抗体水平与发炎关节抗体水平之间的强相关性代表了一项新发现，并为使用血浆发现幼年特发性关节炎自身抗体提供了信心，从而规避了与关节抽吸相关的挑战。我们预计，在 NAPPA 上对 JIA 患者进行自身抗体分析可以产生抗体标记，这些标记可以作为对患者进行分层、预测结果和在分子水平上了解疾病病因的标准。
Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients. A pilot study was performed on the application of a high-throughput platform, the nucleic acid programmable protein array (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from 10 JIA patients was screened for antibodies against 768 proteins on NAPPAs. Quantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r = 0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis. The NAPPAs provide a high-throughput quantitatively reproducible platform to screen for disease-specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPAs could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.
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影响因子：
6.4
作者：
Fattal, Ittai;Shental, Noam;Cohen, Irun R.
通讯作者：
Cohen, Irun R.
影响因子：
2.1
作者：
Shin, J. I.;Kim, K. H.;Kim, D. S.
通讯作者：
Kim, D. S.
影响因子：
--
作者：
Hueber, W;Kidd, BA;Robinson, WH
通讯作者：
Robinson, WH
DOI：
10.1073/pnas.0404848101
发表时间：
2004-10-05
影响因子：
11.1
作者：
Quintana, FJ;Hagedorn, PH;Cohen, IR
通讯作者：
Cohen, IR
影响因子：
2
作者：
Low, Jason M.;Chauhan, Anil K.;Moore, Terry L.
通讯作者：
Moore, Terry L.