Rheumatoid arthritis (RA) is typically preceded by an extended preclinical period where circulating autoantibodies, particularly anti-citrullinated protein antibodies (ACPA), are detectable in the absence of clinical arthritis. Increased dietary intake of anti-inflammatory omega-3 (ω3) polyunsaturated fatty acids (PUFA) has been shown to be associated with a lower the risk of developing incident RA in large epidemiological studies. It is currently not known how changes in fatty acid (FA) metabolism may impact on the progression towards RA in at-risk individuals. To begin to address this question, we profiled serum FAs and oxylipins in an established cohort of at-risk ACPA-positive first-degree relatives (FDR) of RA patients (N = 31), some of whom developed RA (N = 4), and compared their profile to ACPA-negative FDR from the same population (N = 10). Gas chromatography (GC) was used for FA quantitation. Oxylipins were extracted and quantified using high-performance liquid chromatography–tandem mass spectrometry (HPLC/MS/MS). Although we did not detect any meaningful differences in overall FA content between ACPA + and ACPA − FDR, the levels of oxylipins derived from FA metabolism demonstrated significant differences between the two groups, with the ACPA + group demonstrating enrichment in circulating arachidonic acid- and eicosapentaenoic acid-derived molecules. Compared with the ACPA − FDR group, the ACPA + FDR, including those who progressed into inflammatory arthritis, displayed higher levels of LOX-derived oxylipins. ACPA seropositivity in otherwise unaffected individuals at-risk for developing future RA based on family history (FDR) is associated with alterations in the serum oxylipin profile that suggests dysregulated LOX activity.

中文翻译：

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脂氧合酶衍生的氧脂素在抗瓜氨酸蛋白抗体 (ACPA) 阳性、有患类风湿性关节炎风险的个体中含量丰富

类风湿性关节炎（RA）之前通常有一个延长的临床前阶段，在没有临床关节炎的情况下，可以检测到循环自身抗体，特别是抗瓜氨酸蛋白抗体（ACPA）。大型流行病学研究表明，增加膳食中抗炎 omega-3 (ω3) 多不饱和脂肪酸 (PUFA) 的摄入量与降低发生 RA 的风险相关。目前尚不清楚脂肪酸（FA）代谢的变化如何影响高危个体的 RA 进展。为了开始解决这个问题，我们分析了 RA 患者 (N = 31) 的高危 ACPA 阳性一级亲属 (FDR) 队列中的血清 FA 和氧脂素，其中一些患者患有 RA (N = 4) ，并将其概况与同一人群的 ACPA 阴性 FDR 进行比较 (N = 10)。气相色谱 (GC) 用于 FA 定量。使用高效液相色谱-串联质谱法 (HPLC/MS/MS) 提取并定量 Oxylipins。尽管我们没有检测到 ACPA + 和 ACPA − FDR 之间的总 FA 含量有任何有意义的差异，但来自 FA 代谢的氧脂素水平在两组之间表现出显着差异，其中 ACPA + 组表现出循环花生四烯酸和二十碳五烯酸的富集。酸衍生的分子。与ACPA-FDR组相比，ACPA+FDR组，包括那些进展为炎性关节炎的组，显示出更高水平的LOX衍生的氧脂素。根据家族史 (FDR)，在其他未受影响的个体中，ACPA 血清阳性有未来发展为 RA 的风险，这与血清氧脂素谱的变化有关，这表明 LOX 活性失调。