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多种自身抗体在系统性红斑狼疮患者体内形成肾小球免疫沉积物。

Multiple autoantibodies form the glomerular immune deposits in patients with systemic lupus erythematosus.

作者信息

Mannik Mart, Merrill Cynthia E, Stamps Louis D, Wener Mark H

机构信息

Division of Rheumatology, Department of Medicine, University of Washington, Seattle 98195-6428, USA.

出版信息

J Rheumatol. 2003 Jul;30(7):1495-504.

Abstract

OBJECTIVE

To determine the specific antibodies present in glomerular immune deposits in patients with systemic lupus erythematosus (SLE).

METHODS

Kidney tissue was obtained at autopsy and stored frozen until used. Glomeruli were isolated from the renal cortex, sonicated, and the glomerular basement membrane fragments were extracted with a pH 2.5 buffer or 6 M guanidine hydrochloride. The latter method provided a higher yield and was used in most of the 23 specimens studied. The extracted IgG was quantified by a capture assay using an ELISA with chemiluminescence. IgG antibodies to 14 different antigens were quantified by the same type of assay. The enrichment of antibodies in the extracts was determined in comparison to the initial supernatant of glomeruli that served as a serum surrogate.

RESULTS

Antibodies to dsDNA, the collagen-like region of C1q, Sm, SSA, SSB, and chromatin were enriched in glomerular extracts, mainly from patients with proliferative lupus glomerulonephritis. The IgG binding to histones resulted from the presence of immune or non-immune aggregates of IgG. In some specimens all 6 of the above-listed antibodies were enriched. In one specimen antibodies to myeloperoxidase were enriched. Antibodies to cathepsin G, lactoferrin, and beta2-glycoprotein I were not detected. Antibodies to Epstein-Barr viral capsid antigen and nuclear antigen 1 and antibodies to tetanus toxoid were detected in the serum surrogate, but were not enriched in extracts of glomerular basement membrane fragments.

CONCLUSION

Autoantibodies with multiple different specificities form the immune deposits in glomeruli of patients with SLE, including antibodies to dsDNA, Sm, SSA, SSB, the collagen-like region of C1q, and chromatin.

摘要

目的

确定系统性红斑狼疮(SLE)患者肾小球免疫沉积物中存在的特异性抗体。

方法

尸检获取肾脏组织并冷冻保存直至使用。从肾皮质分离肾小球,超声处理后,用pH 2.5缓冲液或6 M盐酸胍提取肾小球基底膜片段。后一种方法产量更高,在研究的23个标本中的大多数都采用了该方法。通过使用化学发光酶联免疫吸附测定(ELISA)的捕获测定法定量提取的IgG。通过相同类型的测定法定量针对14种不同抗原的IgG抗体。与作为血清替代物的肾小球初始上清液相比,确定提取物中抗体的富集情况。

结果

双链DNA(dsDNA)、C1q的胶原样区域、Sm、SSA、SSB和染色质的抗体在肾小球提取物中富集,主要来自增殖性狼疮性肾小球肾炎患者。IgG与组蛋白的结合是由于IgG免疫或非免疫聚集体的存在。在一些标本中,上述所有6种抗体都有富集。在一个标本中,髓过氧化物酶抗体有富集。未检测到组织蛋白酶G、乳铁蛋白和β2糖蛋白I的抗体。在血清替代物中检测到爱泼斯坦-巴尔病毒衣壳抗原和核抗原1的抗体以及破伤风类毒素的抗体,但在肾小球基底膜片段提取物中未富集。

结论

具有多种不同特异性的自身抗体形成SLE患者肾小球中的免疫沉积物,包括针对dsDNA、Sm、SSA、SSB、C1q的胶原样区域和染色质的抗体。

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