Department of Orthopaedic Surgery, University of California, San Diego, La Jolla, California, United States of America.
Department of Obstetrics & Gynecology, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2023 Oct 24;18(10):e0291967. doi: 10.1371/journal.pone.0291967. eCollection 2023.
BACKGROUND: Antibodies to citrullinated protein antigens have been linked to altered left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA). Serum reactivity to several citrullinated protein/peptide antigens has been identified in RA, which are detectable years before RA onset and in individuals who may never develop RA. Among community-living individuals without heart failure (HF) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated associations between serum reactivity to citrullinated protein/peptide antigens, LV mass, LV ejection fraction (LVEF), and incident HF. METHODS: Among 1232 MESA participants, we measured serum reactivity to 28 different citrullinated proteins/peptides using a multiplex bead-based array. Each antibody was defined as having extremely high reactivity (EHR) if >95th percentile cut-off in MESA. Number of EHR antibody responses to citrullinated protein/peptide antigens were summed for each participant (range 0-28). LV mass(g) and LVEF(%) were measured on cardiac MRI. Associations between EHR antibodies and LV mass and LVEF were evaluated using linear regression. Cox proportional hazards models were used to evaluate associations between EHR antibodies and incident HF during 11 years of follow-up, adjusting for age, gender, race/ethnicity, smoking status, systolic blood pressure, use of anti-hypertensive medications, self-reported arthritis, IL-6, body surface area, and estimated glomerular filtration rate. RESULTS: Mean age was 65±10, 50% were female, 40% were White, 21% were Black, 26% were Hispanic/Latino, and 14% were Chinese. Twenty-seven percent of MESA participants had extremely high reactivity to ≥ 1 citrullinated protein/peptide antigen. In fully adjusted analysis, every additional EHR antibody was significantly associated with 0.1% lower LVEF (95% CI: -0.17%, -0.02%). No association was observed with LV mass (β per additional EHR antibody) = 0.13±0.15 (p = 0.37)). Neither the presence nor number of EHR antibodies was associated with incident HF during follow-up (HR per additional EHR antibody = 1.008 (95% CI: 0.97, 1.05)). CONCLUSION: Greater number of extremely highly reactive antibodies was associated with lower LVEF, but not with LV mass or incident HF. Thus, serum reactivity to citrullinated protein/peptide antigens was associated with subtle subclinical changes in myocardial contractility, but the significance in relation to clinically apparent HF is uncertain.
背景：抗瓜氨酸化蛋白抗体与类风湿关节炎（RA）患者左心室（LV）结构和功能的改变有关。在 RA 患者中已经鉴定出几种瓜氨酸化蛋白/肽抗原的血清反应性，这些反应性在 RA 发病前数年和可能永远不会发生 RA 的个体中即可检测到。在多民族动脉粥样硬化研究（MESA）基线时无心力衰竭（HF）的社区居民中，我们研究了血清对瓜氨酸化蛋白/肽抗原的反应性与 LV 质量、LV 射血分数（LVEF）和 HF 事件之间的相关性。
方法：在 1232 名 MESA 参与者中，我们使用基于微珠的多重分析方法测量了血清对 28 种不同瓜氨酸化蛋白/肽的反应性。如果 MESA 中超过 95%的截定点，则将每个抗体定义为具有极高的反应性（EHR）。每个参与者的瓜氨酸化蛋白/肽抗原的 EHR 抗体反应数相加（范围 0-28）。使用心脏 MRI 测量 LV 质量（g）和 LVEF（%）。使用线性回归评估 EHR 抗体与 LV 质量和 LVEF 之间的相关性。在 11 年的随访期间，使用 Cox 比例风险模型评估 EHR 抗体与 HF 事件之间的相关性，调整因素包括年龄、性别、种族/民族、吸烟状况、收缩压、使用抗高血压药物、自述关节炎、IL-6、体表面积和估计肾小球滤过率。
结果：平均年龄为 65±10 岁，50%为女性，40%为白人，21%为黑人，26%为西班牙裔/拉丁裔，14%为中国人。27%的 MESA 参与者对≥1 种瓜氨酸化蛋白/肽抗原具有极高的反应性。在完全调整的分析中，每增加一个 EHR 抗体与 LVEF 降低 0.1%显著相关（95%CI：-0.17%，-0.02%）。与 LV 质量无相关性（每增加一个 EHR 抗体的β）=0.13±0.15（p=0.37））。在随访期间，EHR 抗体的存在或数量均与 HF 事件无关（每增加一个 EHR 抗体的 HR）=1.008（95%CI：0.97，1.05））。
结论：更多的高度反应性抗体与较低的 LVEF 相关，但与 LV 质量或 HF 事件无关。因此，血清对瓜氨酸化蛋白/肽抗原的反应性与心肌收缩力的亚临床变化有关，但与明显的 HF 相关的意义尚不确定。
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