Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity.
Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity.
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狼疮中可溶性MER的循环水平反映了单核细胞/巨噬细胞，自身抗体特异性和疾病活动的M2C激活。
DOI：
10.1186/ar4407
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发表时间：
2013
影响因子：
4.9
通讯作者：
Cohen PL
中科院分区：
文献类型：
--
作者：
Zizzo G;Guerrieri J;Dittman LM;Merrill JT;Cohen PL
系统性红斑狼疮（SLE）的特征是红细胞增多和先天免疫异常激活。我们询问MER受体酪氨酸激酶（MerTK）和AXL脱落到可溶性胞外域是否与SLE的免疫学和临床方面有关。采用酶联免疫吸附法（ELISA）检测107例SLE患者和45例正常对照者血浆sMER和sAXL水平。在40例连续SLE患者中，我们研究了sMER或sAXL与血浆sCD 163（M2活化的标志物）水平之间的潜在相关性。在各种免疫条件下培养的单核细胞/巨噬细胞的上清液中测量所有三种可溶性受体。通过流式细胞术评估MerTK、AXL和CD 163的膜表达。sMER和sAXL均与抗染色质和抗磷脂自身抗体以及血液学和肾脏受累相关。然而，sMER和sAXL彼此之间没有显著相关性; sAXL与生长停滞特异性6（Gas 6）相关，而sMER与游离蛋白S（PROS）水平降低相关。只有sMER与狼疮特异性抗dsDNA、抗Sm、抗核糖核蛋白（抗RNP）和抗Ro 60自身抗体显著相关。发现sMER与疾病活动指数（系统性红斑狼疮疾病活动指数（SLEDAI）、补体减少、循环抗dsDNA滴度）之间存在强相关性，而sAXL则无相关性。与对照组相比，活动性SLEDAI、肾炎、抗dsDNA和抗Ro 60阳性的患者显示更高水平的sMER。sMER（而非sAXL）水平与sCD 163水平相关，而sCD 163水平与SLEDAI相关。sMER和sCD 163的产生发生在“M2 c”极化条件下，而sAXL在I型IFN暴露后释放。抗炎和巨噬细胞“M2 c”单核/巨噬细胞稳态的改变可能在SLE的免疫发病机制中起作用。
Systemic lupus erythematosus (SLE) is characterized by impaired efferocytosis and aberrant activation of innate immunity. We asked if shedding of MER receptor tyrosine kinase (MerTK) and AXL into soluble (s) ectodomains was related to immunological and clinical aspects of SLE. Levels of sMER and sAXL in the plasma of 107 SLE patients and 45 matched controls were measured by ELISA. In 40 consecutive SLE patients, we examined potential correlations between either sMER or sAXL and plasma levels of sCD163, a marker of M2 activation. All three soluble receptors were measured in supernatants of monocytes/macrophages cultured in various immunological conditions. Membrane expression of MerTK, AXL and CD163 was assessed by flow cytometry. Both sMER and sAXL were associated with anti-chromatin and anti-phospholipid autoantibodies, and with hematological and renal involvement. However, sMER and sAXL did not significantly correlate with each other; sAXL correlated with growth arrest-specific 6 (Gas6), whereas sMER correlated with reduced free protein S (PROS) levels. Only sMER showed significant associations with lupus-specific anti-dsDNA, anti-Sm, anti-ribonucleoprotein (anti-RNP) and anti-Ro60 autoantibodies. Strong correlations with disease activity indices (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), complement reduction, titer of circulating anti-dsDNA) were found for sMER, not for sAXL. Patients with active SLEDAI, nephritis, anti-dsDNA and anti-Ro60 positivity showed higher levels of sMER compared to controls. Levels of sMER, not sAXL, correlated with sCD163 levels, and these correlated with SLEDAI. Production of sMER and sCD163 occurred under “M2c” polarizing conditions, whereas sAXL was released upon type-I IFN exposure. Alterations in homeostasis of anti-inflammatory and efferocytic “M2c” monocytes/macrophages may have a role in immunopathogenesis of SLE.
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