Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies.
Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies.
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DOI：
10.1038/srep11888
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发表时间：
2015-07-07
影响因子：
4.6
通讯作者：
Hickey FB
中科院分区：
文献类型：
--
作者：
O'Brien EC;Abdulahad WH;Rutgers A;Huitema MG;O'Reilly VP;Coughlan AM;Harrington M;Heeringa P;Little MA;Hickey FB
ANCA血管炎包括几种自身免疫性疾病，其特征是小血管破坏、呼吸道炎症和肾小球肾炎。大多数患者存在髓过氧化物酶(MPO)或蛋白3(PR3)自身抗体。临床和实验数据表明，发病机制是由ANCA介导的中性粒细胞和单核细胞的激活所驱动的。我们研究了不同的单核细胞亚群的潜在作用。我们发现，与对照组相比，患者中间单核细胞的相对比例增加，并且MPO和PR3在这些细胞上优先表达。我们证明MPO和PR3在单核细胞上相互独立表达，并且PR3与CD177无关。MPO与Fc受体CD16在中间单核细胞上的表达呈正相关。单核细胞亚群对针对MPO和Pr3的抗体的反应不同，抗MPO而不是抗Pr3导致IL-1β、IL-6和IL-8产生增加。与观察到的中间单核细胞表面MPO的高表达一致，这一亚群在抗MPO刺激下产生最高数量的IL-1β。这些数据表明，单核细胞，特别是中间亚群，可能在ANCA血管炎中发挥作用，也表明抗MPO抗体和抗PR3抗体对这些细胞的作用存在显著差异。
ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.
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影响因子：
13.6
作者：
Schreiber, Adrian;Pham, Christine T. N.;Kettritz, Ralph
通讯作者：
Kettritz, Ralph
影响因子：
3.6
作者：
KELLEY, JL;ROZEK, MM;SCHWARTZ, CJ
通讯作者：
SCHWARTZ, CJ
DOI：
10.1038/nri3070
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.5
作者：
CHARLES, LA;FALK, RJ;JENNETTE, JC
通讯作者：
JENNETTE, JC
影响因子：
--
作者：
Rossol, Manuela;Kraus, Stephan;Wagner, Ulf
通讯作者：
Wagner, Ulf