Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases.
Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases.
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DOI：
10.1186/1471-2172-13-16
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发表时间：
2012-04-04
期刊：
影响因子：
3
通讯作者：
Sitaru C
中科院分区：
文献类型：
--
作者：
Licarete E;Ganz S;Recknagel MJ;Di Zenzo G;Hashimoto T;Hertl M;Zambruno G;Hundorfean G;Mudter J;Neurath MF;Bruckner-Tuderman L;Sitaru C
对VII型胶原蛋白的自身免疫通常与皮肤起疱性疾病大疱性表皮松解症（EBA）有关，但也偶尔发生在系统性红斑狼疮或炎症性肠病患者中。本研究的目的是开发一种准确的免疫分析法，用于评估大量患者和健康供体中针对VII型胶原的自身抗体的存在。基于芯片抗原分析和先前的湿润实验室表位定位数据，我们设计了一个嵌合型VII胶原构建体，其中包含了所有具有较高抗原性的VII胶原表位。对EBA （n = 50）、克罗恩病（CD, n = 50）、溃疡性结肠炎（UC, n = 50）、大疱性类天疱疮（BP, n = 76）、寻常性天疱疮（PV, n = 42）和健康供者（n = 245）的血清进行ELISA检测。通过ELISA，受试者工作特征分析的曲线下面积为0.98 (95% CI: 0.9638-1.005)，允许将截止值设置为0.32 OD，计算特异性为98%，灵敏度为94%。优化后的检测结果显示，47例EBA （94%, 95% CI: 87.41% ~ 100%）、2例CD （4%, 95% CI: 0% ~ 9.43%）、8例UC （16%, 95% CI: 5.8% ~ 26%）、2例BP （2.63%, 95% CI: 0% ~ 6.23%）、4例PV （9.52%, 95% CI: 0% ~ 18.4%）患者和4例健康供体（1.63%,95% CI: 0% ~ 3.21%）的血清IgG自身抗体与嵌合蛋白反应。进一步分析显示，IgG1、IgG2、IgG3和IgG4同型血清自身抗体分别有34%、37%、16%和100%识别重组自身抗原。利用嵌合蛋白，我们建立了一种新的、灵敏的、特异的酶联免疫吸附试验来检测胶原蛋白特异性抗体。我们的研究结果显示，在炎症性肠病、天疱疮和大疱性类天疱疮中，胶原- vii特异性自身抗体的患病率较低。此外，我们发现针对VII型胶原的自身免疫反应是由IgG4自身抗体主导的。新的免疫测定法将被证明是临床和转化研究的有用工具，并将改善与vii型胶原特异性自身免疫相关疾病的常规诊断和疾病监测。
Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA), but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50), Crohn's disease (CD, n = 50), ulcerative colitis (UC, n = 50), bullous pemphigoid (BP, n = 76), and pemphigus vulgaris (PV, n = 42) and healthy donors (n = 245). By ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005), allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%), 2 CD (4%; 95% CI: 0%-9.43%), 8 UC (16%; 95% CI: 5.8%-26%), 2 BP (2.63%; 95% CI: 0%-6.23%), and 4 PV (9.52%; 95% CI: 0%-18.4%) patients as well as from 4 (1.63%; 95% CI: 0%-3.21%) healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen. Using a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should prove a useful tool for clinical and translational research and should improve the routine diagnosis and disease monitoring in diseases associated with collagen VII-specific autoimmunity.
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影响因子：
5.3
作者：
Mihai S;Chiriac MT;Herrero-González JE;Goodall M;Jefferis R;Savage CO;Zillikens D;Sitaru C
通讯作者：
Sitaru C
影响因子：
8
作者：
Dignass, A.;Van Assche, G.;Travis, S. P. L.
通讯作者：
Travis, S. P. L.
DOI：
10.4049/jimmunol.1001152
发表时间：
2010-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Luo W;Wang XP;Kashtan CE;Borza DB
通讯作者：
Borza DB
影响因子：
--
作者：
Abrams, Melissa L.;Smidt, Aimee;Mancini, Anthony J.
通讯作者：
Mancini, Anthony J.
影响因子：
4.8
作者：
Borza, DB;Netzer, KO;Hudson, BG
通讯作者：
Hudson, BG