Autoantibodies associated with RNA are more enriched than anti-dsDNA antibodies in circulating immune complexes in SLE
Autoantibodies associated with RNA are more enriched than anti-dsDNA antibodies in circulating immune complexes in SLE
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DOI：
10.1177/0961203311434938
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发表时间：
2012-05-01
期刊：
影响因子：
2.6
通讯作者：
Ronnelid, J.
中科院分区：
文献类型：
--
作者：
Ahlin, E.;Mathsson, L.;Ronnelid, J.
不同的自身抗体在系统性红斑狼疮（SLE）免疫复合物（ic）中积累到何种程度，以及这种积累是否与疾病活动性相关已被研究。采用聚乙二醇（PEG）沉淀法和c1q结合法从SLE血清中分离出ic。自身抗体的特异性通过密度法定量的线印迹测定。为了比较自身抗体的相对水平，将水平归一化为ELISA测定的血清和平行ic中IgG的总水平。样本在横断面设计中进行调查，并与在活动性和非活动性SLE期间获得的样本进行配对设计。与平行血清相比，除抗dsdna外，所有研究的自身抗体特异性在循环ic中都富集。针对rna相关抗原（抗rnp /Sm、抗Sm、抗ssa /Ro60、抗ssa /Ro52、抗ssb /La）的抗体组均比dna相关抗原（抗dsdna、抗组蛋白、抗核小体）或细胞质抗原（抗核糖体P）的中位数富集更高。特别是针对RNP/Sm和SSA/Ro52的自身抗体在SLE PEG沉淀中富集程度最高。这些发现通过分析c1q结合ic的自身抗体含量得到证实。在活动性和非活动性SLE中，所研究的自身抗体的IC积累程度没有差异。我们的研究结果表明，在分离的SLE IC中，针对rna相关自身抗原和dna相关自身抗原的自身抗体在富集程度上存在差异，这表明与针对dna相关自身抗原（如dsDNA）的抗体相比，rna相关自身抗体更容易在SLE中形成循环IC。这些发现有助于理解SLE患者靶器官中差异自身抗体积累的机制。狼疮杂志（2012）21,586-595。
To what extent different autoantibodies accumulate in systemic lupus erythematosus (SLE) immune complexes (ICs), and whether such accumulation is associated with disease activity has been investigated. ICs were isolated from SLE sera by both polyethylene glycol (PEG) precipitation and C1q-binding. Autoantibody specificities were determined using a lineblot assay quantified by densitometry. To compare the relative levels of autoantibodies, levels were normalized to the total levels of IgG measured by ELISA in sera and parallel ICs. Samples were investigated both in a cross-sectional design as well as in a paired design with samples obtained during both active and inactive SLE. All investigated autoantibody specificities except anti-dsDNA were enriched in circulating ICs as compared with parallel sera. The group of antibodies against RNA-associated antigens (anti-RNP/Sm, anti-Sm, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB/La) all exhibited higher median enrichment than the DNA-associated (anti-dsDNA, anti-histones, anti-nucleosomes) or cytoplasmic (anti-ribosomal P) antigens. In particular autoantibodies against RNP/Sm and SSA/Ro52 had the highest degree of enrichment in SLE PEG precipitates. These findings were corroborated by analysis of autoantibody content in C1q-bound ICs. There was no difference in degree of IC accumulation of the investigated autoantibodies during active and inactive SLE. Our findings demonstrate a difference in enrichment between autoantibodies against RNA-and DNA-associated autoantigens in isolated SLE IC, suggesting that the RNA-associated autoantibodies are more prone to form circulating ICs in SLE, in contrast to antibodies against DNA-associated autoantigens such as dsDNA. These finding have implications in understanding mechanisms of differential autoantibody accumulation in target organs in SLE. Lupus (2012) 21, 586-595.