Surface-bound anti-type II collagen-containing immune complexes induce production of tumor necrosis factor α, interleukin-1β, and interleukin-8 from peripheral blood monocytes via Fcγ receptor IIa -: A potential pathophysiologic mechanism for humoral anti-type II collagen immunity in arthritis
Surface-bound anti-type II collagen-containing immune complexes induce production of tumor necrosis factor α, interleukin-1β, and interleukin-8 from peripheral blood monocytes via Fcγ receptor IIa -: A potential pathophysiologic mechanism for humoral anti-type II collagen immunity in arthritis
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DOI：
10.1002/art.21892
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发表时间：
2006-06-01
影响因子：
--
通讯作者：
Ronnelid, Johan
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文献类型：
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作者：
Mullazehi, Mohammed;Mathsson, Linda;Ronnelid, Johan
目标。II型胶原（CII）是透明软骨的主要成分，在类风湿关节炎患者的一个亚群中发现了针对CII的抗体。我们进行了这项研究，以研究针对CII的抗体是否以及如何形成具有细胞因子诱导特性的固相免疫复合物（ICs），在理论上类似于炎症关节的情况，在炎症期间，CII暴露于与抗CII抗体相互作用。在固相IC模型中，对65例具有不同水平的抗天然CII抗体的关节炎患者和10名健康对照进行了抗CII和细胞因子诱导的评估。单核细胞要么被耗尽，要么被富集以定义应答细胞。阻断Fc γ受体的抗体（Fc γ R）被用来确定相关的T细胞表面受体。来自关节炎患者的含有抗cii的ic可诱导肿瘤坏死因子α (TNF α)、白细胞介素-1 ss （IL-1 ss）和IL-8的产生。我们发现酶联免疫吸附法光密度值与TNF α (r = 0.862, P < 0.0001)、IL-1 ss （r = 0.839, P < 0.0001）和IL-8 （r = 0.547, P < 0.0001）的诱导密切相关。细胞因子诱导所需的抗含cii的IC密度阈值在外周血单个核细胞供者之间存在差异。单核细胞耗尽后，含抗cii的ic诱导的细胞因子产生几乎完全被消除（bbb99%），受体阻断研究显示，阻断Fc γ RIIa后，TNF - α、IL-1 ss和IL-8的产生显著减少，而阻断Fc γ riii后则没有。这些发现代表了高水平抗cii关节炎患者亚组关节炎症持续的可能机制。阻断Fc γ RIIa和抑制滑膜巨噬细胞是这类患者可能的治疗选择。
Objective. Type II collagen (CII) is a major component of hyaline cartilage, and antibodies against CII are found in a subgroup of patients with rheumatoid arthritis. We undertook this study to investigate whether and how antibodies directed against CII can form solid-phase immune complexes (ICs) with cytokine-inducing properties in a model theoretically resembling the situation in the inflamed joint, in which CII is exposed for interaction with anti-CII antibodies during periods of inflammation.Methods. Sixty-five arthritis patients with varying levels of anti-native CII antibodies and 10 healthy controls were evaluated concerning anti-CII and cyto-kines induced in a solid-phase IC model. Monocytes were either depleted or enriched to define responder cells. Antibodies blocking Fc gamma receptors (Fc gamma R) were used to define the responsible T cell surface receptors.Results. ICs containing anti-CII from arthritis patients induced the production of tumor necrosis factor alpha(TNF alpha), interieukin-1 ss (IL-1 ss), and IL-8. We found a close correlation between enzyme-linked immunosorbent assay optical density values and induction of TNF alpha (r = 0.862, P < 0.0001), IL-1 ss (r = 0.839, P < 0.0001), and IL-8 (r = 0.547, P < 0.0001). The anti-CII-containing IC density threshold needed for cytokine induction differed among peripheral blood mononuclear cell donors. Anti-CII-containing IC-induced cytokine production was almost totally abolished (> 99%) after monocyte depletion, and receptor blocking studies showed significant decreases in the production of TNF alpha, IL-1 ss, and IL-8 after blocking Fc gamma RIIa, but not after blocking Fc gamma RIII.Conclusion. These findings represent a possible mechanism for perpetuation of joint inflammation in the subgroup of arthritis patients with high levels of anti-CII. Blockade of Fc gamma RIIa and suppression of synovial macrophages are conceivable treatment options in such patients.