Selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto- and microbial antigens
Selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto- and microbial antigens
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DOI：
10.1053/gast.2002.35379
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发表时间：
2002-09-01
期刊：
影响因子：
29.4
通讯作者：
Targan, SR
中科院分区：
文献类型：
--
作者：
Landers, CJ;Cohavy, O;Targan, SR
背景和目标：克罗恩病的先前研究表明，对含有数百种抗原的超声处理细菌制剂的耐受性全面丧失。单相关研究表明，一种单独的细菌可以在一种动物模型中诱导结肠炎，而另一种细菌在其他模型中负责。在克罗恩病患者中，已记录了对微生物和自身抗原（大肠杆菌外膜孔蛋白C和荧光假单胞菌相关序列12的抗体、抗酿酒酵母抗体（ASCA）和核周抗神经细胞胞质抗体）的血清反应。我们的目的是确定是否有这些特异性抗原的异质性反应。方法：对330例克罗恩病患者的血清进行分析。免疫球蛋白A酶联免疫吸附测定ASCA，外膜孔蛋白C，或12和免疫球蛋白G酶联免疫吸附测定ASCA和ANCA确定抗体的存在和水平。免疫荧光法测定核周抗神经细胞胞浆抗体。结果如下：56%的患者检测到ASCA，55%的患者对外膜孔蛋白C有血清反应性，50%的患者对12有血清反应性，23%的患者核周抗神经细胞胞浆抗体阳性。85%的人对至少1种抗原有反应;只有4%的人对所有4种抗原有反应。在微生物抗原中，78%对至少1种有反应，57%为双阳性，但只有26%对所有3种有反应。随着时间的推移和疾病活动的变化，反应水平是稳定的。在具有相同定性抗原应答特征的患者中，定量应答不同。这些抗体反应的聚类分析产生4组：ASCA，外膜孔蛋白Q/12，核周抗神经细胞胞质抗体，或无/低响应。结论：与其说是整体性耐受丧失，不如说是患者亚群对所选微生物和自身抗原的反应不同。
Background & Aims: Previous studies in Crohn's disease suggest global loss of tolerance with sonicated bacteria preparations containing hundreds of antigens. Monoassociation studies show that a solitary bacterium can induce colitis in one animal model, whereas another is responsible in other models. Among patients with Crohn's disease, serum responses have been documented to microbial and autoantigens (antibodies to the Escherichia coli outermembrane porin C and the Pseudomonas fluorescens-associated sequence 12, antisaccharomyces cerevisiae antibody (ASCA), and perinuclear antineutrophil cytoplasmic antibodies). Our aim was to determine whether there are heterogeneous responses to these specific antigens. Methods: Sera from 330 Crohn's patients were analyzed. Immunoglobulin A enzyme-linked immunosorbent assays to ASCA, outer-membrane porin C, or 12 and immunoglobulin G enzyme-linked immunosorbent assay to ASCA and ANCA determined the presence and level of antibodies. Perinuclear antineutrophil cytoplasmic antibodies were determined by immunofluorescence. Results: ASCA was detected in 56% of patients; 55% were seroreactive to outermembrane porin C, 50% were seroreactive to 12, and 23% were perinuclear antineutrophil cytoplasmic antibody positive. Eighty-five percent responded to at least :1 antigen; only 4% responded to all 4. Among microbial antigens, 78% responded to at least 1, and 57% were double positive, but only 26% responded to all 3. The level of response was stable over time and with change in disease activity. Among patients with the same qualitative antigen-response profiles, quantitative response differed. Cluster analysis of these antibody responses yielded 4 groups: ASCA, outer-membrane porin Q/12, perinuclear antineutrophil cytoplasmic antibodies, or no/low response. Conclusions: Rather than global loss of tolerance, there seem to be patient subsets with differing responses to selected microbial and autoantigens.