Andersen Catherine J, Vance Terrence M
Department of Biology, Fairfield University, Fairfield, CT, United States.
Department of Nutritional Sciences, University of Connecticut, Storrs, CT, United States.
Front Med (Lausanne). 2022 May 26;9:887741. doi: 10.3389/fmed.2022.887741. eCollection 2022.
Lipid metabolism contributes to the regulation of leukocyte activity and immune responses, and may serve as a therapeutic target in the pathophysiology and clinical management of autoimmune disorders. In addition to lipid-lowering properties, statins have been shown to exert anti-inflammatory and immunomodulatory effects within the context of autoimmunity. Importantly, autoimmune incidence and lipid markers differ between men and women, suggesting that the relationship between lipid metabolism and immune function may vary by sex. Therefore, we investigated whether a predictive, sex-specific relationship exists between serum lipids, statin use, and antinuclear antibodies (ANA)-a routine clinical marker of autoimmunity and immune dysfunction-in U.S. men and women (>20 years old; = 1,526) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Within this population, a greater proportion of women were positive for ANA (ANA+) and had higher ANA titers, as compared to men. While we did not observe statistical differences in average total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), or triglyceride levels in ANA positive (ANA+) vs. ANA negative (ANA-) men or women, we observed that a greater proportion of ANA+ women had high total cholesterol levels (>240 mg/dL) when compared to ANA+ men (13.0 vs. 9.0%), and that a greater percentage of ANA+ women had low HDL-C as compared to ANA+ men (29.2 vs. 19.6%). However, in logistic regression models, total cholesterol, LDL-C, and HDL-C levels were not able to predict ANA status, whereas elevated serum triglycerides (150 to < 200 mg/dL) were significantly less likely to be ANA+ vs. ANA- (OR 0.33; 95% CI 0.11-0.92) in men only. Interestingly, women who reported taking statins have significantly lower odds of being ANA+ (OR 0.25; 95% CI 0.09-0.76), whereas no significant association between statin use and ANA status was observed in men. Together, our findings provide novel insight into the relationship between lipid metabolism and autoimmunity by elucidating the limited, albeit sex-specific utility of routine clinical serum lipid levels to predict ANA status at the population level, while further identifying a sex-specific and protective role for statins in predicting ANA status in women.
脂质代谢有助于调节白细胞活性和免疫反应，可能成为自身免疫性疾病病理生理学和临床管理中的一个治疗靶点。除了降脂特性外，他汀类药物已被证明在自身免疫背景下具有抗炎和免疫调节作用。重要的是，自身免疫发病率和脂质标志物在男性和女性之间存在差异，这表明脂质代谢与免疫功能之间的关系可能因性别而异。因此，我们调查了在美国国家健康与营养检查调查（NHANES）1999 - 2004年中年龄大于20岁的1526名男性和女性中，血清脂质、他汀类药物使用与抗核抗体（ANA）（自身免疫和免疫功能障碍的常规临床标志物）之间是否存在预测性的、性别特异性的关系。在该人群中，与男性相比，ANA阳性（ANA +）的女性比例更高且ANA滴度更高。虽然我们未观察到ANA阳性（ANA +）与ANA阴性（ANA -）的男性或女性在平均总胆固醇、低密度脂蛋白胆固醇（LDL - C）、高密度脂蛋白胆固醇（HDL - C）或甘油三酯水平上存在统计学差异，但我们观察到，与ANA +男性相比，ANA +女性中总胆固醇水平高（>240 mg/dL）的比例更高（13.0%对9.0%），且与ANA +男性相比，ANA +女性中HDL - C低的百分比更高（29.2%对19.6%）。然而，在逻辑回归模型中，总胆固醇、LDL - C和HDL - C水平无法预测ANA状态，而仅在男性中，血清甘油三酯升高（150至<200 mg/dL）时ANA +的可能性显著低于ANA -（OR 0.33；95% CI 0.11 - 0.92）。有趣的是，报告服用他汀类药物的女性ANA +的几率显著更低（OR 0.25；95% CI 0.09 - 0.76），而在男性中未观察到他汀类药物使用与ANA状态之间存在显著关联。总之，我们的研究结果通过阐明常规临床血清脂质水平在人群水平预测ANA状态方面有限但性别特异性的效用，为脂质代谢与自身免疫之间的关系提供了新的见解，同时进一步确定了他汀类药物在预测女性ANA状态方面的性别特异性保护作用。
