New centromere autoantigens identified in systemic sclerosis using centromere protein microarrays.

New centromere autoantigens identified in systemic sclerosis using centromere protein microarrays.
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使用着丝粒蛋白微阵列在系统性硬化症中鉴定出新的着丝粒自身抗原

DOI:
10.3899/jrheum.120264
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发表时间:
2013-04
期刊:
The Journal of rheumatology
影响因子:
--
通讯作者:
Wu L
Wu L
中科院分区:
其他
文献类型:
--
作者:
Song G;Hu C;Zhu H;Wang L;Zhang F;Li Y;Wu L

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鉴定抗着丝粒抗体(ACA)作用于着丝粒蛋白(CENP)的新靶点,并探讨其与系统性硬化症(SSc)临床表现的关系。通过点样14个纯化的CENP制备CENP聚焦蛋白质微阵列。将这些微阵列与35份ACA阳性SSc血清和20份ACA阴性健康对照样品单独孵育。选择新鉴定的具有高灵敏度的CENP自身抗原进行验证和表征。统计学分析显示,11个CENP是SSc患者ACA的潜在靶抗原。其中CENP-P、CENP-Q、CENP-M(亚型I)、CENP-J和CENP-T 5种为新的,其中CENP-P和CENP-Q在ACA阳性SSc血清中显示出高敏感性,分别为34.3%和28.6%。随后,186份SSc血清(35份ACA阳性和151份阴性)、69份来自其他各种自身免疫性疾病(原发性舍格伦综合征、系统性红斑狼疮、类风湿性关节炎和原发性胆汁性肝硬化)的ACA阳性血清和31份健康血清通过ELISA检测抗CENP-P和-Q自身抗体的存在,然后进行Western印迹分析。CENP-P和-Q自身抗体在各疾病组ACA阳性血清中均有检出,其中SSc的检出率最高。151例ACA阴性血清中有9例检出抗CENP-P抗体。与临床信息的相关性分析显示,在ACA阳性队列中,抗CENP-P阳性患者的IgG、伊加和红细胞沉降率水平较高,而在ACA阴性SSc患者中,抗CENP-P阳性患者更容易发生肾脏疾病。无论ACA状态如何,抗CENP-P或Q阴性患者似乎主要受间质性肺病影响。CENP-P和CENP-Q被鉴定为新的ACA自身抗原CENP微阵列检测,随后通过ELISA和Western印迹验证。两者均对间质性肺疾病有预后价值。在ACA阴性队列中,CENP-P与肾脏疾病相关。
To identify novel centromere protein (CENP) targets of anticentromere antibodies (ACA), and to investigate their association with clinical manifestations of systemic sclerosis (SSc). A CENP-focused protein microarray was fabricated by spotting 14 purified CENP. These microarrays were individually incubated with 35 ACA-positive SSc sera and 20 ACA-negative healthy control samples. Newly identified CENP autoantigens with high sensitivities were selected for validation and characterization. Statistical analysis revealed 11 CENP are potential target antigens of ACA in patients with SSc. Of them, 5 [CENP-P, CENP-Q, CENP-M (isoform I), CENP-J, and CENP-T] are novel, among which CENP-P and CENP-Q showed high sensitivities in ACA-positive SSc sera of 34.3% and 28.6%, respectively. Subsequently, 186 SSc sera (35 ACA-positives and 151 negatives), 69 ACA-positive sera from other various autoimmune diseases (primary Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis), and 31 healthy sera were assayed for the presence of anti-CENP-P and -Q autoantibodies by ELISA followed by Western blotting analysis. CENP-P and -Q autoantibodies were detected in ACA-positive sera of various disease groups; among them, SSc showed the highest detection rate. Anti-CENP-P was also found in 9 of the 151 ACA-negative sera. Analyses of the correlation with clinical information showed anti-CENP-P-positive patients had higher levels of IgG, IgA, and erythrocyte sedimentation rate among the ACA-positive cohort and were more vulnerable to renal disease in the ACA-negative patients with SSc. Regardless of ACA status, anti-CENP-P or Q-negative patients seem to be predominantly affected by interstitial lung disease. CENP-P and CENP-Q were identified as novel ACA autoantigens by CENP microarray assays followed by validation of ELISA and Western blotting. Both of them have prognostic utility for interstitial lung disease. CENP-P was associated with renal disease in an ACA-negative cohort.
DOI: 10.1002/hep.21472
发表时间: 2007-01-01
期刊: HEPATOLOGY
影响因子: 13.5
作者:
Nakamura, Minoru;Kondo, Hisayoshi;Ishibashi, Hiromi
通讯作者: Ishibashi, Hiromi
DOI: 10.1007/s00296-004-0568-4
发表时间: 2006-02-01
影响因子: 4
作者:
Hsu, TC;Chang, CH;Tsay, GJ
通讯作者: Tsay, GJ
DOI: 10.1007/s10067-005-0005-4
发表时间: 2006-05-01
影响因子: 3.4
作者:
Pakunpanya, K;Verasertniyom, O;Janwityanujit, S
通讯作者: Janwityanujit, S
DOI: 10.1016/j.autrev.2008.06.010
发表时间: 2008-09-01
影响因子: 13.6
作者:
Koenig, Martial;Dieude, Melanie;Senecal, Jean-Luc
通讯作者: Senecal, Jean-Luc
DOI: 10.1016/0002-9343(80)90462-3
发表时间: 1980-01-01
影响因子: 5.9
作者:
FRITZLER, MJ;KINSELLA, TD
通讯作者: KINSELLA, TD