Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis.
Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis.
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DOI：
10.1002/art.38307
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发表时间：
2014-04
影响因子：
13.3
通讯作者：
Robinson, William H.
中科院分区：
文献类型：
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作者：
Sokolove, Jeremy;Johnson, Dannette S.;Lahey, Lauren J.;Wagner, Catriona A.;Cheng, Danye;Thiele, Geoffrey M.;Michaud, Kaleb;Sayles, Harlan;Reimold, Andreas M.;Caplan, Liron;Cannon, Grant W.;Kerr, Gail;Mikuls, Ted R.;Robinson, William H.
类风湿因子(RF)和抗瓜氨酸蛋白抗体(ACPA)在类风湿关节炎(RA)中的共存被很好地描述。然而，这两种不同的自身抗体之间潜在相互作用的机制还没有很好地确定。我们试图评估ACPA和RF与疾病活动性以及类风湿关节炎相关炎症指标的流行病学和分子相互作用。在1,488名退伍军人RA队列中，比较了双阴性(ACCP-/RF-)、ACPA阳性与RF阴性(ACCP+/RF-)、ACPA阴性与RF阳性(ACCP-/RF+)或双阳性(ACCP+/RF+)亚组的疾病活动性、血清细胞因子水平和多重ACPA水平。此外，研究还使用了体外免疫复合物(IC)刺激试验，其中巨噬细胞与ACPA-IC在存在或不存在单抗IgMRF的情况下孵育，并测量肿瘤坏死因子α的产生作为巨噬细胞激活的读数。与双阴性亚组(以及各单阳性亚组)相比，ACCP+/RF+亚组的疾病活动性、血清C反应蛋白和炎性细胞因子均较高(均P<0.001)。与单用ACPA-ICs相比，ACPA-ICs体外刺激巨噬细胞可诱导细胞因子的产生增加(P=0.003)。ACPA和Ig MRF的联合存在可在体外介导促炎细胞因子的产生，并与RA全身炎症和疾病活动性增加有关。我们的数据表明，IgM RF增强了ACPA-ICs刺激巨噬细胞因子产生的能力，从而提供了一条RF增强ACPA-ICs在RA中致病的机制。
The co-occurrence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) is well described in rheumatoid arthritis (RA). However, the mechanisms underlying the potential interaction between these two distinct autoantibodies has not been well defined. We sought to evaluate the epidemiologic and molecular interaction of ACPA and RF with both disease activity as well as measures of RA-associated inflammation. In a cohort of 1,488 Veterans with RA, measures of disease activity and levels of serum cytokines and multiplex ACPA were compared between the double-negative (aCCP-/RF-), ACPA-positive and RF-negative (aCCP+/RF-), ACPA-negative and RF-positive (aCCP-/RF+), or double-positive (aCCP+/RF+) subgroups. Studies were additionally performed using an in vitro immune complex (IC) stimulation assay in which macrophages were incubated with ACPA-ICs in the presence or absence of monoclonal IgM RF, and TNFα production measured as readout of macrophage activation. Compared with the double negative (as well each single positive) subgroup, the aCCP+/RF+ subgroup exhibited higher disease activity, serum CRP, and inflammatory cytokines (all P<0.001). In vitro stimulation of macrophages by ACPA-ICs induced increased cytokine production with the addition of monoclonal IgM RF as compared to ACPA-ICs alone (P=0.003) The combined presence of ACPA and IgM RF mediates increased proinflammatory cytokine production in vitro, and is associated with increased systemic inflammation and disease activity in RA. Our data suggest that IgM RF enhances the capacity of ACPA-ICs to stimulate macrophage cytokine production, thereby providing a mechanistic link by which RF enhances the pathogenicity of ACPA-ICs in RA.
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影响因子：
4.9
作者：
Mikuls TR;Gould KA;Bynoté KK;Yu F;Levan TD;Thiele GM;Michaud KD;O'Dell JR;Reimold AM;Hooker R;Caplan L;Johnson DS;Kerr G;Richards JS;Cannon GW;Criswell LA;Noble JA;Bridges SL Jr;Hughes L;Gregersen PK
通讯作者：
Gregersen PK
影响因子：
--
作者：
BALESTRIERI, G;TINCANI, A;BOMBARDIERI, S
通讯作者：
BOMBARDIERI, S
影响因子：
15.9
作者：
Kuhn, KA;Kulik, L;Holers, VM
通讯作者：
Holers, VM
影响因子：
27.4
作者：
Hueber, Wolfgang;Tomooka, Beren H.;Robinson, William H.
通讯作者：
Robinson, William H.
影响因子：
3.4
作者：
Silveira, I. G.;Burlingame, R. W.;Staub, H. L.
通讯作者：
Staub, H. L.