Breaking tolerance to double stranded DNA, nucleosome, and other nuclear antigens is not required for the pathogenesis of lupus glomerulonephritis.
Breaking tolerance to double stranded DNA, nucleosome, and other nuclear antigens is not required for the pathogenesis of lupus glomerulonephritis.
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狼疮性肾小球炎的发病机理不需要对双链DNA，核小体和其他核抗原的破坏耐受性。
DOI：
10.1084/jem.20031519
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发表时间：
2004-01-19
影响因子：
15.3
通讯作者：
Fu, SM
中科院分区：
文献类型：
--
作者：
Waters, ST;McDuffie, M;Bagavant, H;Deshmukh, US;Gaskin, F;Jiang, C;Tung, KSK;Fu, SM
在狼疮易感的NZM 2328小鼠中，1号染色体上的Cgnz 1基因座与慢性肾小球肾炎、严重蛋白尿和雌性早期死亡有关。4号染色体上的Adnz 1位点与抗核抗体（ANA）和抗双链DNA（dsDNA）抗体（Ab）的产生相关。在本研究中，两个同源株，NZM2328.C57L/Jc 1（NZM.C57Lc1）和NZM2328.C57L/Jc 4（NZM.C57Lc4），通过替换各自的遗传区间含有Cgnz 1或Adnz 1与那些从C57 L/J，一个nonlupus-prone株。NZM.C57Lc1雌性动物慢性肾小球肾炎和重度蛋白尿的发生率显著降低。NZM.C57Lc4雌性动物患有慢性肾小球肾炎和重度蛋白尿，无循环ANA、抗dsDNA和抗核小体Ab。这些数据证实了连锁分析。出乎意料的是，NZM.C57Lc1雌性几乎没有抗dsDNA和相关Ab，表明1号染色体上存在第二个基因座Adnz 2。通过免疫荧光和电子显微镜观察，患病的NZM.C57Lc4肾脏具有免疫复合物。这些肾脏的洗脱液不含ANA、抗dsDNA和抗核小体Ab，表明存在非抗dsDNA致肾炎Ab。因此，破坏对dsDNA和染色质的耐受性不是狼疮性肾炎的发病机制所必需的。这些结果再次证实，抗dsDNA和相关抗体的产生和慢性肾小球肾炎是独立的遗传控制。这些发现对系统性红斑狼疮的发病机制有重要意义。
In lupus-prone NZM2328 mice, a locus Cgnz1 on chromosome 1 was linked to chronic glomerulonephritis, severe proteinuria, and early mortality in females. A locus Adnz1 on chromosome 4 was linked to antinuclear antibody (ANA) and anti–double stranded DNA (dsDNA) antibody (Ab) production. In this investigation, two congenic strains, NZM2328.C57L/Jc1 (NZM.C57Lc1) and NZM2328.C57L/Jc4 (NZM.C57Lc4), were generated by replacing the respective genetic intervals containing either Cgnz1 or Adnz1 with those from C57L/J, a nonlupus-prone strain. The NZM.C57Lc1 females had markedly reduced incidence of chronic glomerulonephritis and severe proteinuria. NZM.C57Lc4 females had chronic glomerulonephritis and severe proteinuria without circulating ANA, anti-dsDNA, and antinucleosome Ab. These data confirm the linkage analysis. Unexpectedly, NZM.C57Lc1 females had little anti-dsDNA and related Ab, suggesting the presence of a second locus Adnz2 on chromosome 1. The diseased NZM.C57Lc4 kidneys had immune complexes by immunofluorescence and electron microscopy. The eluates from these kidneys did not contain ANA, anti-dsDNA, and antinucleosome Ab, indicative of the presence of non–anti-dsDNA nephritogenic Ab. Thus, breaking tolerance to dsDNA and chromatin is not required for the pathogenesis of lupus nephritis. These results reaffirm that anti-dsDNA and related Ab production and chronic glomerulonephritis are under independent genetic control. These findings have significant implications in the pathogenesis of systemic lupus erythematosus.
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影响因子：
4.4
作者：
Deocharan, B;Qing, XP;Putterman, C
通讯作者：
Putterman, C
影响因子：
15.3
作者：
KOFFLER, D;CARR, R;KUNKEL, HG
通讯作者：
KUNKEL, HG
影响因子：
4.4
作者：
Singh, RR;Saxena, V;Jacob, CO
通讯作者：
Jacob, CO
DOI：
10.1084/jem.189.10.1639
发表时间：
1999-05-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan OT;Hannum LG;Haberman AM;Madaio MP;Shlomchik MJ
通讯作者：
Shlomchik MJ
DOI：
10.1084/jem.179.5.1445
发表时间：
1994-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fang Q;Kannapell CC;Gaskin F;Solomon A;Koopman WJ;Fu SM
通讯作者：
Fu SM