Leidinger Petra, Keller Andreas, Heisel Sabrina, Ludwig Nicole, Rheinheimer Stefanie, Klein Veronika, Andres Claudia, Hamacher Jürg, Huwer Hanno, Stephan Bernhard, Stehle Ingo, Lenhof Hans-Peter, Meese Eckart
Department of Human Genetics, Medical School, Saarland University, Building 60, 66421 Homburg/Saar, Germany.
Respir Res. 2009 Mar 12;10(1):20. doi: 10.1186/1465-9921-10-20.
Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients.
An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera.
By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity.
The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.
慢性阻塞性肺疾病(COPD)是一种具有自身免疫特征(包括IgG自身抗体)的呼吸道炎症性疾病。在本研究中,我们分析了自身抗体反应的复杂性,并揭示了COPD患者自身抗体所识别的抗原的性质。
建立了一个包含1827个网格化免疫原性肽克隆的阵列,并用17例COPD患者的血清和60例健康对照进行筛选。通过目视检查和最近开发的计算机辅助图像分析技术对蛋白质阵列进行评估。通过这种计算机辅助图像分析技术,我们计算了每个肽克隆和每个血清的强度值,并计算了每个克隆的受试者操作特征曲线(AUC)下的面积以及COPD血清与对照血清之间的分离度。
通过目视评估,我们检测到381个与COPD患者自身抗体反应的肽克隆,其中17个克隆与超过60%的COPD血清反应,7个克隆与超过90%的COPD血清反应。通过自动图像分析系统对COPD血清和对照进行比较,确定了212个具有信息性AUC值的肽克隆。通过计算机序列分析,我们发现了先前与免疫原性相关的序列基序的富集。
在COPD患者中鉴定出相当复杂的体液免疫反应,支持了COPD是一种具有强烈自身免疫特征的疾病的观点。鉴定新的免疫原性抗原是更好地理解COPD自身免疫成分的第一步。