Immunosciences Lab, Inc. 822 S. Robertson Blvd, Ste 312, Los Angeles, CA 90035, USA.
Department of Preventive Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
Int J Mol Sci. 2020 Feb 18;21(4):1381. doi: 10.3390/ijms21041381.
Individuals with intestinal barrier dysfunction are more prone to autoimmunity. Lipopolysaccharides (LPS) from gut bacteria have been shown to play a role in systemic inflammation, leading to the opening of the gut and blood-brain barrier (BBB). This study aims to measure antibodies against LPS and barrier proteins in samples positive for anti- antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) and compare them with these same antibodies in controls to determine whether a correlation between LPS and barrier proteins could be found. We obtained 94 ASCA- and 94 ANCA-positive blood samples, as well as 188 blood samples from healthy controls. Samples were assessed for antibodies to LPS, zonulin+occludin, S100B, and aquaporin-4 (AQP4). Results show significant elevation in antibodies in about 30% of ASCA- and ANCA-positive sera and demonstrate positive linear relationships between these antibodies. The findings suggest that individuals positive for ASCA and ANCA have increased odds of developing intestinal and BBB permeability compared to healthy subjects. The levels of LPS antibodies in both ASCA- and ANCA-positive and negative specimens showed from low and moderate to high correlation with antibodies to barrier proteins. This study shows that LPS, by damaging the gut and BBBs, contribute to the extra-intestinal manifestation of IBD. We conclude that IBD patients should be screened for LPS antibodies in an effort to detect or prevent possible barrier damage at the earliest stage possible to abrogate disease symptoms in IBS and associated disorders.
具有肠道屏障功能障碍的个体更容易发生自身免疫。来自肠道细菌的脂多糖 (LPS) 已被证明在全身炎症中起作用，导致肠道和血脑屏障 (BBB) 的开放。本研究旨在测量抗抗体 (ASCA) 和抗中性粒细胞胞质抗体 (ANCA) 阳性样本中针对 LPS 和屏障蛋白的抗体，并将其与对照中的这些相同抗体进行比较，以确定是否可以发现 LPS 和屏障蛋白之间的相关性。我们获得了 94 份 ASCA 和 94 份 ANCA 阳性的血液样本，以及 188 份来自健康对照者的血液样本。样本评估了针对 LPS、zonulin+occludin、S100B 和水通道蛋白-4 (AQP4) 的抗体。结果显示，大约 30%的 ASCA 和 ANCA 阳性血清中的抗体显著升高，并显示出这些抗体之间存在正线性关系。研究结果表明，与健康受试者相比，ASCA 和 ANCA 阳性个体发生肠道和 BBB 通透性增加的可能性更大。在 ASCA 和 ANCA 阳性和阴性标本中，LPS 抗体的水平与屏障蛋白的抗体呈从低到中至高的相关性。这项研究表明，LPS 通过破坏肠道和 BBB，导致 IBD 的肠外表现。我们得出结论，IBD 患者应筛查 LPS 抗体，以尽早发现可能的屏障损伤，从而消除 IBS 和相关疾病的症状。
