Department of Neuroscience, Psychiatry, Uppsala University, Uppsala University Hospital, Entrance 10, Floor 3B, 751 85 Uppsala, Sweden.
Department of Protein Science, Affinity Proteomics, Science for life laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
Psychoneuroendocrinology. 2021 Apr;126:105162. doi: 10.1016/j.psyneuen.2021.105162. Epub 2021 Feb 4.
Growing evidence implies interactions between infections, the immune system and vulnerability for psychiatric disease. This study applies an affinity proteomic-based method to investigate potential disease associated autoantibody signatures in serum from patients from the "Young Adults" section of the Department of General Psychiatry at Uppsala University Hospital (n = 395) and population-based controls (n = 102). We found serum levels of antibodies against Lipopolysaccharide Binding Protein (LBP), a protein that is important for mediating innate immune responses involving the toll-like receptor-4 (TLR-4), to be higher in patients compared to controls (Mann Whitney U-test p = 5.248 × 10). The patients were divided into three groups based on their relative levels of autoantibodies against LBP. The distribution of autism spectra disorders (p = 2.0 × 10) and hospital care for an infection as adults (p = 0.036) differed between the anti-LBP groups, with low incidence in the group of patients with the highest levels of anti-LBP who were diagnosed with primarily affective and anxiety disorders. In a sub-group analysis, the controls who screened positive for current or previous psychiatric diagnosis (n = 20) had higher anti-LBP compared to non-psychiatric controls with negative screening for psychiatric disorders (Mann Whitney U-test p = 0.006). Inflammatory markers were found to differ across anti-LBP groups and several pro-inflammatory markers, including IL-1β, were low in patients with high anti-LBP and serum LBP levels were lowest in patients with the highest levels of antibodies against LBP (p = 3.5 × 10). A cell-based model showed that polyclonal rabbit anti-LBP, obtained through purification via the same protein fragment used in the initial autoantibody analysis, could interfere with LBP signaling since addition of anti-LBP to the assay reduced both IL-1β and IL-6 release from activated monocytes in response to LBP and LPS (p = 0.0001 and p = 0.02). This novel finding of antibodies against LBP, where high levels were only found in young adults with psychiatric disease, merits further study. Our results suggest that these antibodies may have relevance for TLR4 based immune responses and vulnerability for both infection and psychiatric disorders.
越来越多的证据表明感染、免疫系统和精神疾病易感性之间存在相互作用。本研究应用基于亲和蛋白质组学的方法，在乌普萨拉大学医院普通精神病学部的“年轻成年人”部分的患者（n=395）和基于人群的对照组（n=102）的血清中，研究潜在的与疾病相关的自身抗体特征。我们发现，与对照组相比，患者血清中脂多糖结合蛋白（LBP）的抗体水平更高（Mann Whitney U 检验，p=5.248×10）。LBP 自身抗体水平相对较高的患者被分为三组。LBP 抗体组之间的自闭症谱系障碍（p=2.0×10）和成年后因感染住院的分布（p=0.036）不同，LBP 抗体水平最高的患者组主要诊断为情感和焦虑障碍，发病率较低。在亚组分析中，筛查出当前或以前有精神科诊断的对照组（n=20）与未筛查出精神障碍的非精神病对照组相比，抗 LBP 水平更高（Mann Whitney U 检验，p=0.006）。在抗 LBP 组之间发现了不同的炎症标志物，包括白细胞介素 1β在内的几种促炎标志物在高抗 LBP 患者中较低，而高抗 LBP 患者的血清 LBP 水平最低（p=3.5×10）。细胞模型显示，通过最初自身抗体分析中使用的相同蛋白片段进行纯化获得的多克隆兔抗 LBP 可以干扰 LBP 信号，因为向测定中添加抗 LBP 可减少 LBP 和 LPS 激活的单核细胞释放白细胞介素 1β和白细胞介素 6（p=0.0001 和 p=0.02）。在患有精神疾病的年轻成年人中仅发现高水平的抗 LBP 抗体的这一新发现值得进一步研究。我们的结果表明，这些抗体可能与 TLR4 相关的免疫反应以及感染和精神疾病的易感性有关。
