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通过用致病性自身抗体的基于互补决定区1(CDR1)和互补决定区3(CDR3)的肽进行治疗,预防(新西兰黑鼠×新西兰白鼠)F1小鼠的系统性红斑狼疮样疾病。

Prevention of systemic lupus erythematosus-like disease in (NZBxNZW)F1 mice by treating with CDR1- and CDR3-based peptides of a pathogenic autoantibody.

作者信息

Eilat E, Zinger H, Nyska A, Mozes E

机构信息

Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.

出版信息

J Clin Immunol. 2000 Jul;20(4):268-78. doi: 10.1023/a:1006663519132.

DOI:10.1023/a:1006663519132
PMID:10939714
Abstract

Two peptides based on the complementarity-determining regions (CDR) of a pathogenic murine anti-DNA antibody were employed in an attempt to prevent the spontaneous systemic lupus erythematosus (SLE)-like disease of (NZBxNZW)F1 mice. Female mice, at the age of 2 months, were injected with either the CDR1- or the CDR3-based peptides (pCDR1, pCDR3) subcutaneously or intravenously in aqueous solution for a total of 8-10 treatments. A reduction was observed in the total and pathogenic IgG2a and IgG3 anti-DNA antibody titers in the CDR-treated groups. Treatment reduced the number of mice that developed proteinuria and immune complex deposits in their kidneys. The severity of renal pathology was significantly reduced in the pCDR3 (P<0.02) and pCDR1 (P< or = 0.05) treated mice. Thus, both CDR-based peptides administered in aqueous solution were capable of preventing the SLE-like disease in (NZBxNZW)F1 mice, although the beneficial effects of pCDR3 appeared to be more pronounced than those of pCDR1 in the treated mice.

摘要

基于致病性小鼠抗DNA抗体互补决定区(CDR)的两种肽被用于尝试预防(NZBxNZW)F1小鼠的自发性系统性红斑狼疮(SLE)样疾病。2月龄雌性小鼠分别皮下或静脉注射基于CDR1或CDR3的肽(pCDR1、pCDR3)的水溶液,共进行8至10次治疗。在接受CDR治疗的组中,总抗DNA抗体以及致病性IgG2a和IgG3抗DNA抗体滴度均有所降低。治疗减少了出现蛋白尿和肾脏免疫复合物沉积的小鼠数量。在接受pCDR3(P<0.02)和pCDR1(P≤0.05)治疗的小鼠中,肾脏病理严重程度显著降低。因此,两种基于CDR的肽在水溶液中给药均能够预防(NZBxNZW)F1小鼠的SLE样疾病,尽管在接受治疗的小鼠中,pCDR3的有益效果似乎比pCDR1更显著。

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本文引用的文献

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A peptide derived from a polyreactive monoclonal anti-DNA natural antibody can modulate lupus development in (NZBxNZW)F1 mice.一种源自多反应性抗DNA天然单克隆抗体的肽可调节(NZBxNZW)F1小鼠的狼疮发展。
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Spontaneous autoimmune disease in (NZB x NZW)F1 mice is ameliorated by treatment with methimazole.
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Innate and humoral recognition of the products of cell death: differential antigenicity and immunogenicity in lupus.细胞死亡产物的固有和体液识别:狼疮中的差异抗原性和免疫原性
Clin Exp Immunol. 2017 Mar;187(3):353-368. doi: 10.1111/cei.12889. Epub 2016 Dec 5.
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CD20-Mimotope Peptide Active Immunotherapy in Systemic Lupus Erythematosus and a Reappraisal of Vaccination Strategies in Rheumatic Diseases.CD20 模拟肽主动免疫治疗红斑狼疮及风湿性疾病疫苗接种策略再评价。
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Role of MHC class I molecules in autoimmune disease.MHC I类分子在自身免疫性疾病中的作用。
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Molecular properties of anti-DNA induced in preautoimmune NZB/W mice by immunization with bacterial DNA.通过用细菌DNA免疫在自身免疫前NZB/W小鼠中诱导产生的抗DNA的分子特性。
J Immunol. 1997 May 1;158(9):4500-6.
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