Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Front Immunol. 2023 Jul 20;14:1199727. doi: 10.3389/fimmu.2023.1199727. eCollection 2023.
The relationship between metabolic and inflammatory pathways play a pathogenic role in various cardiometabolic disorders and is potentially also involved in the pathogenesis of other disorders such as cancer, autoimmunity and infectious diseases. Common variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults, characterized by increased frequency of airway infections with capsulated bacteria. In addition, a large proportion of CVID patients have autoimmune and inflammatory complications associated with systemic inflammation. We summarize the evidence that support a role of a bidirectional pathogenic interaction between inflammation and metabolic disturbances in CVID. This include low levels and function of high-density lipoprotein (HDL), high levels of triglycerides (TG) and its major lipoprotein very low-density lipoprotein (VLDL), and an unfavorable fatty acid (FA) profile. The dysregulation of TG, VLDL and FA were linked to disturbed gut microbiota profile, and TG and VLDL levels were strongly associated with lipopolysaccharides (LPS), a marker of gut leakage in blood. Of note, the disturbed lipid profile in CVID did not include total cholesterol levels or high low-density lipoprotein levels. Furthermore, increased VLDL and TG levels in blood were not associated with diet, high body mass index and liver steatosis, suggesting a different phenotype than in patients with traditional cardiovascular risk such as metabolic syndrome. We hypothesize that these metabolic disturbances are linked to inflammation in a bidirectional manner with disturbed gut microbiota as a potential contributing factor.
代谢和炎症途径之间的关系在各种代谢紊乱中起着致病作用，并且可能也与其他疾病的发病机制有关，如癌症、自身免疫和传染病。普通可变免疫缺陷（CVID）是成人中最常见的原发性免疫缺陷，其特征是呼吸道感染荚膜细菌的频率增加。此外，很大一部分 CVID 患者存在与全身炎症相关的自身免疫和炎症并发症。我们总结了支持炎症和代谢紊乱之间存在双向致病相互作用的证据，这包括高密度脂蛋白（HDL）水平低和功能障碍、甘油三酯（TG）及其主要脂蛋白极低密度脂蛋白（VLDL）水平升高，以及不利的脂肪酸（FA）谱。TG、VLDL 和 FA 的失调与肠道微生物群谱紊乱有关，并且 TG 和 VLDL 水平与脂多糖（LPS）强烈相关，LPS 是血液中肠道渗漏的标志物。值得注意的是，CVID 中的脂质失调不包括总胆固醇水平或高 LDL 水平。此外，血液中增加的 VLDL 和 TG 水平与饮食、高体重指数和肝脂肪变性无关，这表明与代谢综合征等传统心血管风险患者的表型不同。我们假设这些代谢紊乱以双向方式与炎症相关，肠道微生物群紊乱是潜在的促成因素。
