Prüßmann Wiebke, Prüßmann Jasper, Koga Hiroshi, Recke Andreas, Iwata Hiroaki, Juhl David, Görg Siegfried, Henschler Reinhard, Hashimoto Takashi, Schmidt Enno, Zillikens Detlef, Ibrahim Saleh M, Ludwig Ralf J
Department of Dermatology, University of Lübeck, Lübeck, Germany.
Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany.
Orphanet J Rare Dis. 2015 May 15;10:63. doi: 10.1186/s13023-015-0278-x.
Mucocutaneous blistering is characteristic of autoimmune bullous dermatoses (AIBD). Blisters are caused by autoantibodies directed against structural components of the skin. Hence, detection of specific autoantibodies has become a hallmark for AIBD diagnosis. Studies on prevalence of AIBD autoantibodies in healthy individuals yielded contradictory results.
To clarify this, samples from 7063 blood donors were tested for presence of anti-BP180-NC16A, anti-BP230 and anti-Dsg1/3 IgG by indirect immunofluorescence (IF) microscopy using a biochip.
Cumulative prevalence of these autoantibodies was 0.9 % (CI: 0.7-1.1 %), with anti-BP180-NC16A IgG being most prevalent. Validation of IF findings using ELISA confirmed presence of autoantibodies in 7/15 (anti-Dsg1), 6/7 (anti-Dsg3), 35/37 (anti-BP180-NC16A) and 2/3 (anti-BP230) cases. Moreover, in 16 samples, anti-BP180-NC16A autoantibody concentrations exceeded the cut-off for the diagnosis of bullous pemphigoid. Interestingly, these anti-BP180-NC16A autoantibodies from healthy individuals formed immune complexes with recombinant antigen and dose-dependently activated neutrophils in vitro. However, fine-epitope mapping within NC16A showed a different binding pattern of anti-BP180-NC16A autoantibodies from healthy individuals compared to bullous pemphigoid patients, while IgG subclasses were identical.
Collectively, we here report a low prevalence of AIBD autoantibodies in a large cohort of healthy individuals. Furthermore, functional analysis shows differences between autoantibodies from healthy donors and AIBD patients.
皮肤黏膜水疱形成是自身免疫性大疱性皮肤病（AIBD）的特征。水疱由针对皮肤结构成分的自身抗体引起。因此，检测特异性自身抗体已成为AIBD诊断的标志。关于健康个体中AIBD自身抗体患病率的研究结果相互矛盾。
为阐明这一点，使用生物芯片通过间接免疫荧光（IF）显微镜检测了7063名献血者样本中抗BP180-NC16A、抗BP230和抗桥粒芯糖蛋白1/3 IgG的存在情况。
这些自身抗体的累积患病率为0.9%（置信区间：0.7 - 1.1%），其中抗BP180-NC16A IgG最为常见。使用酶联免疫吸附测定（ELISA）对IF结果进行验证，证实15例中有7例（抗桥粒芯糖蛋白1）、7例中有6例（抗桥粒芯糖蛋白3）、37例中有35例（抗BP180-NC16A）和3例中有2例（抗BP230）存在自身抗体。此外，在16个样本中，抗BP180-NC16A自身抗体浓度超过了大疱性类天疱疮诊断的临界值。有趣的是，来自健康个体的这些抗BP180-NC16A自身抗体在体外与重组抗原形成免疫复合物，并剂量依赖性地激活中性粒细胞。然而，NC16A内的精细表位图谱显示，与大疱性类天疱疮患者相比，健康个体的抗BP180-NC16A自身抗体具有不同的结合模式，而IgG亚类相同。
总体而言，我们在此报告了一大群健康个体中AIBD自身抗体的低患病率。此外，功能分析显示健康供体和AIBD患者的自身抗体之间存在差异。
