Activated complement components and complement activator molecules on the surface of cell-derived microparticles in patients with rheumatoid arthritis and healthy individuals
Activated complement components and complement activator molecules on the surface of cell-derived microparticles in patients with rheumatoid arthritis and healthy individuals
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DOI：
10.1136/ard.2006.061309
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发表时间：
2007-08-01
影响因子：
27.4
通讯作者：
Hack, C. Erik
中科院分区：
文献类型：
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作者：
Biro, Eva;Nieuwland, Rienk;Hack, C. Erik
目的：在体外，微粒可以通过经典途径激活补体。如果离体证实，这种机制可能有助于类风湿性关节炎（RA）的发病机制。因此，我们研究了RA患者和健康个体的细胞衍生微粒表面上活化的补体成分和补体激活剂分子的存在。采用流式细胞术分析10例RA患者滑液（n = 8）和血浆（n = 9）以及10例性别和年龄匹配的健康人血浆中的微粒结合补体成分结果：RA患者关节液中含有大量结合C1 q、C4和/或C3的微粒，而RA患者血浆和对照组血浆中的含量较低。结合C1 q的微粒与滑液中结合C3的微粒相关（r = 0.961，p = 0.0001），与血浆中结合C4的微粒相关（RA：r = 0.908，p = 0.0007;对照：r = 0.632，p = 0.0498），表明经典途径激活。在滑液中，IgM和IgG微粒与C1 q微粒相关（r = 0.728，p = 0.0408; r = 0.952，p = 0.0003），在血浆中，CRP微粒与C1 q微粒相关（RA：r = 0.903，p = 0.0021;对照：r = 0.683，p = 0.0296），表明IgG和IgM参与RA滑液中经典途径的激活，CRP参与血浆中低水平经典途径的激活。本研究证明了在离体微粒上存在结合的补体成分和激活剂分子，并支持它们在血浆中低水平补体激活和RA滑液中补体激活增加中的作用。
Objectives: In vitro, microparticles can activate complement via the classical pathway. If demonstrable ex vivo, this mechanism may contribute to the pathogenesis of rheumatoid arthritis (RA). We therefore investigated the presence of activated complement components and complement activator molecules on the surface of cell-derived microparticles of RA patients and healthy individuals.Methods: Microparticles from synovial fluid (n = 8) and plasma (n = 9) of 10 RA patients and plasma of sex-and age-matched healthy individuals (n = 10) were analysed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules (C- reactive protein (CRP), serum amyloid P component (SAP), immunoglobulin (Ig) M, IgG).Results: Microparticles with bound C1q, C4, and/or C3 were abundant in RA synovial fluid, while in RA and control plasma much lower levels were present. Microparticles with bound C1q correlated with those with bound C3 in synovial fluid (r = 0.961, p = 0.0001), and with those with bound C4 in plasma (RA: r = 0.908, p = 0.0007; control: r = 0.632, p = 0.0498), indicating classical pathway activation. In synovial fluid, microparticles with IgM and IgG correlated with those with C1q (r = 0.728, p = 0.0408; r = 0.952, p = 0.0003, respectively), and in plasma, microparticles with CRP correlated with those with C1q (RA: r = 0.903, p = 0.0021; control: r = 0.683, p = 0.0296), implicating IgG and IgM in the classical pathway activation in RA synovial fluid, and CRP in the low level classical pathway activation in plasma.Conclusions: This study demonstrates the presence of bound complement components and activator molecules on microparticles ex vivo, and supports their role in low grade complement activation in plasma and increased complement activation in RA synovial fluid.