Immunization with a peptide surrogate for double-stranded DNA (dsDNA) induces autoantibody production and renal immunoglobulin deposition.
Immunization with a peptide surrogate for double-stranded DNA (dsDNA) induces autoantibody production and renal immunoglobulin deposition.
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双链DNA（DSDNA）的肽替代物免疫可诱导自身抗体的产生和肾脏免疫球蛋白沉积。
DOI：
10.1084/jem.188.1.29
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发表时间：
1998-07-06
影响因子：
15.3
通讯作者：
Diamond, B
中科院分区：
文献类型：
--
作者：
Putterman, C;Diamond, B
抗双链DNA（dsDNA）抗体是系统性红斑狼疮（SLE）特有的血清学异常，可能在疾病的发病机制中起重要作用。尽管SLE中存在的抗dsDNA抗体表明抗原驱动的应答，但尚未最终确定抗原。通过筛选噬菌体肽展示文库，我们先前证明了十肽DWEYSVWLSN被致病性鼠IgG 2b抗dsDNA抗体R4 A特异性结合。为了研究蛋白抗原可能触发狼疮样自身免疫的可能性，我们用佐剂中的DWEYSVWLSN免疫BALB/c小鼠。小鼠在初次免疫后2-3周产生显著滴度的IgG抗dsDNA抗体。免疫小鼠还产生了抗其他狼疮自身抗原的抗体，49 d时肾小球中出现免疫球蛋白沉积。尽管在BALB/c小鼠中对肽和dsDNA的免疫反应很明显，但在其他近交系小鼠中几乎没有反应。这项研究表明，狼疮样抗dsDNA反应可以产生在nonautoimmune小鼠免疫肽抗原。肽诱导的自身免疫可能有助于了解SLE中抗原特异性的传播。然而，最重要的是，肽抗原可以启动SLE样免疫反应的证明打开了可能触发SLE的潜在抗原刺激的新篇章。
Anti–double-stranded DNA (dsDNA) antibodies are the serologic abnormality characteristically associated with systemic lupus erythematosus (SLE) and may play an important role in disease pathogenesis. Although the anti-dsDNA antibodies present in SLE are indicative of an antigen-driven response, the antigen has not been conclusively identified. By screening a phage peptide display library, we demonstrated previously that the decapeptide DWEYSVWLSN is specifically bound by the pathogenic murine IgG2b anti-dsDNA antibody R4A. To investigate the possibility that a protein antigen might trigger lupus-like autoimmunity, we immunized BALB/c mice with DWEYSVWLSN in adjuvant. Mice developed significant titers of IgG anti-dsDNA antibodies 2–3 wk after the initial immunization. Immunized mice also developed antibodies against some other lupus autoantigens, and immunoglobulin deposition was present in renal glomeruli at 49 d. Although an immune response to peptide and dsDNA was evident in BALB/c mice, there was little response in other inbred strains. This study demonstrates that lupus-like anti-dsDNA reactivity can be generated in nonautoimmune mice by immunization with a peptide antigen. Peptide-induced autoimmunity may prove useful in understanding the spreading of antigenic specificities targeted in SLE. However, most importantly, the demonstration that a peptide antigen can initiate a SLE-like immune response opens a new chapter on the potential antigenic stimuli that might trigger SLE.
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影响因子：
4.4
作者：
OHNISHI, K;EBLING, FM;TSAO, BP
通讯作者：
TSAO, BP
影响因子：
15.9
作者：
GRAYZEL, A;SOLOMON, A;DIAMOND, B
通讯作者：
DIAMOND, B
DOI：
10.1073/pnas.85.7.2260
发表时间：
1988-04-01
影响因子：
11.1
作者：
MENDLOVIC, S;BROCKE, S;MOZES, E
通讯作者：
MOZES, E
影响因子：
15.9
作者：
Putterman, C;Limpanasithikul, W;Diamond, B
通讯作者：
Diamond, B
影响因子：
3.6
作者：
DESAYMARD, C;GIUSTI, AM;SCHARFF, MD
通讯作者：
SCHARFF, MD