Immune complexes from rheumatoid arthritis synovial fluid induce FcgammaRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-alpha by peripheral blood mononuclear cells.
Immune complexes from rheumatoid arthritis synovial fluid induce FcgammaRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-alpha by peripheral blood mononuclear cells.
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DOI：
10.1186/ar1926
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发表时间：
2006
影响因子：
4.9
通讯作者：
Rönnelid J
中科院分区：
文献类型：
--
作者：
Mathsson L;Lampa J;Mullazehi M;Rönnelid J
免疫复合物（IC）可以通过Fc受体诱导外周血单个核细胞产生细胞因子。在许多临床和实验环境中，风湿因子（RF）响应于IC而产生。我们研究了聚乙二醇（PEG）沉淀类风湿关节炎（RA）血清和滑液（SF）中的IC是否以及如何影响外周血单个核细胞产生细胞因子。我们还研究了RF和IC诱导的细胞因子产生之间的关系。将来自47名RA患者和来自15名健康对照个体的平行血清和SF进行PEG沉淀。将沉淀物加入无血清外周血单核细胞培养物中，20小时后测量肿瘤坏死因子（TNF）-α水平。在单独的细胞培养实验中，FcγRIIa和FcγRIII被阻断，单核细胞被耗尽或富集。通过比浊法测定血清中的RF，并使用ELISA测定沉淀物中的IgG水平和血清中的抗环瓜氨酸肽抗体。从患者病历中收集临床数据。在两项独立的研究中，我们证明了RF、PEG沉淀的IgG水平与PEG沉淀的SF IC诱导的促炎细胞因子TNF-α之间的相关性。血清IC无相关性。由SF沉淀物而非血清沉淀物诱导的TNF-α水平与肿胀和压痛关节的数量相关。单核细胞/巨噬细胞是主要的应答细胞，阻断FcγRIIa（但不阻断FcγRIII）可抑制沉淀IC刺激培养物中TNF-α的产生。抗环瓜氨酸肽与RF相关，但与PEG沉淀物中的IgG含量或沉淀物诱导的TNF-α水平无关。这些发现支持了SF IC和相关RF产生与RA中的精氨酸依赖性炎症直接相关的假设。抑制RA关节中的单核细胞/巨噬细胞或阻断灵长类特异性活化FcγRIIa受体可能是减少血清阳性RA患者关节中IC诱导的TNF-α产生的方法。
Immune complexes (ICs) can induce production of cytokines by peripheral blood mononuclear cells via Fc receptors. Rheumatoid factor (RF) develop in response to ICs in many clinical and experimental settings. We investigated whether and how polyethylene glycol (PEG) precipitated ICs from rheumatoid arthritis (RA) sera and synovial fluid (SF) can influence cytokine production by peripheral blood mononuclear cells. We also examined the relationship between RF and IC induced cytokine production. Parallel sera and SF from 47 RA patients and sera from 15 healthy control individuals were PEG precipitated. The precipitates were added to serum-free peripheral blood mononuclear cell cultures and tumour necrosis factor (TNF)-α levels were measured after 20 hours. In separate cell culture experiments FcγRIIa and FcγRIII were blocked and monocytes were depleted or enriched. RF in serum was determined by nephelometry, and IgG levels in precipitates and anti-cyclic citrullinated peptide antibodies in serum were measured using ELISA. Clinical data were collected from the patients' charts. In two separate investigations, we demonstrated a correlation between RF, PEG-precipitated IgG levels and induction of the proinflammatory cytokine TNF-α by PEG-precipitated SF ICs. No such correlation was found for serum ICs. TNF-α levels induced by SF precipitates, but not serum precipitates, correlated with the number of swollen and tender joints. Monocytes/macrophages were shown to be the main responder cells, and blockade of FcγRIIa, but not blockade of FcγRIII, inhibited TNF-α production in cultures stimulated with precipitated ICs. Anti-cyclic citrullinated peptide correlated with RF but exhibited no association with IgG content in PEG precipitates or with precipitate-induced TNF-α levels. These findings support the hypothesis that SF ICs and correlated RF production are directly linked to cytokine-dependent inflammation in RA. Suppression of monocytes/macrophages in RA joints or blockade of the primate-specific activating FcγRIIa receptor might be ways to reduce IC-induced TNF-α production in the joints of seropositive RA patients.
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影响因子：
27.4
作者：
Forslind, K;Ahlmén, M;Svensson, B
通讯作者：
Svensson, B
影响因子：
4.6
作者：
Tejde, A;Mathsson, L;Rönnelid, J
通讯作者：
Rönnelid, J
影响因子：
8.6
作者：
Jarvis, JN;Xu, CS;del Rio, AQ
通讯作者：
del Rio, AQ
影响因子：
2.2
作者：
PONTESDECARVALHO, LC;LANNESVIEIRA, J;GALVAOCASTRO, B
通讯作者：
GALVAOCASTRO, B
影响因子：
4
作者：
ANTES, U;HEINZ, HP;LOOS, M
通讯作者：
LOOS, M