Table_1_The Alternative Complement Pathway Is Activated Without a Corresponding Terminal Pathway Activation in Patients With Heart Failure.docx

ObjectiveDysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B (FB) and the C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with HF.
MethodsWe analyzed plasma levels of FB, C3bBbP, and terminal C5b-9 complement complex (TCC) in 343 HF patients and 27 healthy controls.
ResultsCompared with controls, patients with HF had elevated levels of circulating FB (1.6-fold, p < 0.001) and C3bBbP (1.3-fold, p < 0.001). In contrast, TCC, reflecting the terminal pathway, was not significantly increased (p = 0.15 vs controls). FB was associated with NT-proBNP, troponin, eGFR, and i.e., C-reactive protein. FB, C3bBbP and TCC were not associated with mortality in HF during a mean follow up of 4.3 years.
ConclusionOur findings suggest that in patients with HF, the alternative pathway is activated. However, this is not accompanied by activation of the terminal pathway.

研究目的：补体系统（complement system）失调在心力衰竭（heart failure, HF）患者中已有报道，但目前针对补体旁路途径的相关研究数据仍较为匮乏，且尚不明确此类患者体内B因子（factor B, FB）及C3转化酶C3bBbP的水平是否升高。本研究假设，心力衰竭患者的血浆FB与C3bBbP水平将与疾病严重程度及生存结局相关。
研究方法：本研究纳入343例心力衰竭患者与27名健康对照者，检测其血浆中FB、C3bBbP及末端补体复合物C5b-9（terminal C5b-9 complement complex, TCC）的水平。
研究结果：与健康对照者相比，心力衰竭患者的循环FB水平升高1.6倍（p < 0.001），C3bBbP水平升高1.3倍（p < 0.001）。与之相反，反映末端补体途径激活的TCC水平无显著升高（与对照组相比p = 0.15）。FB水平与N末端B型利钠肽原（NT-proBNP）、肌钙蛋白、估算肾小球滤过率（eGFR），即C反应蛋白相关。在平均4.3年的随访期间，心力衰竭患者的FB、C3bBbP及TCC水平均与死亡率无显著关联。
研究结论：本研究结果表明，心力衰竭患者体内的补体旁路途径被激活，但并未伴随末端补体途径的激活。