Hendrikx Tim, Watzenböck Martin L, Walenbergh Sofie M A, Amir Shahzada, Gruber Sabrina, Kozma Maria Ozsvar, Grabsch Heike I, Koek Ger H, Pierik Marieke J, Staufer Katharina, Trauner Michael, Kalhan Satish C, Jonkers Daisy, Hofker Marten H, Binder Christoph J, Shiri-Sverdlov Ronit
Departments of Molecular Genetics, Pathology, and Internal Medicine, Division of Gastroenterology and Hepatology, School of Nutrition and Translational Research in Metabolism (NUTRIM) and School of Oncology and Developmental Biology (GROW), Maastricht University and Maastricht University Medical Center (MUMC), PO Box 616, 6200 MD, Maastricht, The Netherlands.
Departments of Laboratory Medicine, Surgery, and Internal Medicine III, Division of Gastroenterology And Hepatology, Medical University of Vienna, Vienna, Austria.
BMC Med. 2016 Jul 22;14(1):107. doi: 10.1186/s12916-016-0652-0.
Lipid oxidation of membrane phospholipids is accompanied by the formation of oxidation-specific epitopes (OSE). These epitopes are recognized by specific antibodies and represent danger-associated molecular patterns that are generated during chronic inflammatory processes. In a murine model for hepatic inflammation during non-alcoholic fatty liver disease (NAFLD), increased antibody levels targeting OSE were found to be protective. Here, our aim was to determine an association between OSE-specific antibody titers and NAFLD in humans.
IgM and IgG levels with specificity for various OSE were assessed in the plasma of patients with NAFLD (n = 71) and healthy controls (n = 68). Antibody titers were comprehensively analyzed in patients with NAFLD after classification by histological evaluation of liver biopsies. Statistical analysis was performed to determine significant correlations and odds ratios. To study the specificity for NAFLD, plasma antibody titers were measured in patients with hepatitis C (n = 40) and inflammatory bowel disease (n = 62).
IgM titers against OSE were lower in patients with NAFLD compared to controls. Further biopsy-based classification of patients with NAFLD did not show any difference in IgM levels. Plasma IgM titers towards the P1 mimotope demonstrated an inverse correlation with markers for obesity, systemic inflammation, and liver damage. In contrast, hepatitis C and increased disease activity during inflammatory bowel disease was not associated with reduced IgM titers.
Our data highlight the importance of immune recognition of OSE by IgM antibodies in the pathophysiology of NAFLD.
膜磷脂的脂质氧化伴随着氧化特异性表位（OSE）的形成。这些表位可被特异性抗体识别，代表了在慢性炎症过程中产生的危险相关分子模式。在非酒精性脂肪性肝病（NAFLD）期间肝脏炎症的小鼠模型中，发现靶向OSE的抗体水平升高具有保护作用。在此，我们的目的是确定人类中OSE特异性抗体滴度与NAFLD之间的关联。
在NAFLD患者（n = 71）和健康对照者（n = 68）的血浆中评估对各种OSE具有特异性的IgM和IgG水平。在通过肝活检的组织学评估进行分类后，对NAFLD患者的抗体滴度进行了全面分析。进行统计分析以确定显著相关性和优势比。为了研究对NAFLD的特异性，在丙型肝炎患者（n = 40）和炎症性肠病患者（n = 62）中测量了血浆抗体滴度。
与对照组相比，NAFLD患者中针对OSE的IgM滴度较低。基于活检对NAFLD患者进行的进一步分类未显示IgM水平有任何差异。针对P1模拟表位的血浆IgM滴度与肥胖、全身炎症和肝损伤标志物呈负相关。相比之下，丙型肝炎和炎症性肠病期间疾病活动增加与IgM滴度降低无关。
我们的数据突出了IgM抗体对OSE的免疫识别在NAFLD病理生理学中的重要性。
