The Influence of an Elastase-Sensitive Complement C5 Variant on Lupus Nephritis and Its Flare.
The Influence of an Elastase-Sensitive Complement C5 Variant on Lupus Nephritis and Its Flare.
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弹性酶敏感的补体C5变体对狼疮肾炎及其耀斑的影响。
DOI：
10.1016/j.ekir.2021.05.029
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发表时间：
2021-08
影响因子：
6
通讯作者：
Birmingham DJ
中科院分区：
文献类型：
--
作者：
Toy CR;Song H;Nagaraja HN;Scott J;Greco J;Zhang X;Yu CY;Tumlin JA;Rovin BH;Hebert LA;Birmingham DJ
存在C5多态性（rs17611,2404g >A），其中G等位基因与中性粒细胞弹性酶增强的c5a样蛋白产生相关。这项队列研究探讨了这种多态性作为狼疮性肾炎（LN）的危险因素，以及对狼疮性肾炎发作期间C5a和膜攻击复合体（MAC）水平的影响。对一组狼疮患者（n = 155）进行2404G >a多态性基因分型。纵向LN亚群（n = 66）在非肾性或LN发作前4个月和/或2个月检测血浆和尿液中C5a和MAC水平。2404G等位基因和2404-GG基因型与黑人狼疮患者的LN相关，而与白人狼疮患者无关。在纵向队列中，无论2404G>A基因型或种族如何，尿和血浆C5a水平在非肾病发作时都没有改变。尿（而非血浆）C5a水平在LN耀斑时升高，与种族无关，2404-GG患者的C5a水平更高，其中30例LN耀斑中有8例C5a水平非常高。较高的蛋白尿和血清肌酐水平也发生在这8个耀斑。2404-GG患者的尿（而非血浆）MAC水平也在LN发作时升高，并与尿C5a水平相关。C5 2404-G等位基因/GG基因型是黑色狼疮患者LN的潜在危险因素。GG基因型与尿C5a和MAC水平的急剧增加有关，这些尿C5a和MAC水平在LN耀斑亚组中对应于较高的LN疾病指数。血浆中缺乏相应的变化表明这些增加反映了肾内补体活化。
A C5 polymorphism (rs17611, 2404G>A) exists where the G allele associates with enhanced C5a-like production by neutrophil elastase. This cohort study investigated the influence of this polymorphism as a risk factor for lupus nephritis (LN), and on C5a and membrane attack complex (MAC) levels in LN during flare. A cohort of lupus patients (n = 155) was genotyped for the 2404G>A polymorphism. A longitudinal LN subset (n = 66) was tested for plasma and urine levels of C5a and MAC 4 and/or 2 months before and at nonrenal or LN flare. The 2404G allele and 2404-GG genotype were associated with LN in black, but not white, lupus patients. In the longitudinal cohort, neither urine nor plasma C5a levels changed at nonrenal flare regardless of 2404G>A genotype or race. Urine (but not plasma) C5a levels increased at LN flare independent of race, more so in 2404-GG patients where 8 of 30 LN flares exhibited very high C5a levels. Higher proteinuria and serum creatinine levels also occurred in these eight flares. Urine (but not plasma) MAC levels also increased at LN flare in 2404-GG patients and correlated with urine C5a levels. The C5 2404-G allele/GG genotype is a potential risk factor for LN uniquely in black lupus patients. The GG genotype is associated with sharp increases in urine C5a and MAC levels in a subset of LN flares that correspond to higher LN disease indices. The lack of corresponding changes in plasma suggests these increases reflect intrarenal complement activation.
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DOI：
10.4049/jimmunol.0903678
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Amara U;Flierl MA;Rittirsch D;Klos A;Chen H;Acker B;Brückner UB;Nilsson B;Gebhard F;Lambris JD;Huber-Lang M
通讯作者：
Huber-Lang M
DOI：
10.4049/jimmunol.1402956
发表时间：
2015-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Giles JL;Choy E;van den Berg C;Morgan BP;Harris CL
通讯作者：
Harris CL
影响因子：
15.9
作者：
Woehrl, Bianca;Brouwer, Matthijs C.;van de Beek, Diederik
通讯作者：
van de Beek, Diederik
影响因子：
3.5
作者：
Xu, Ke;Peng, Hui;Ye, Dong-Qing
通讯作者：
Ye, Dong-Qing
DOI：
10.2215/cjn.03990415
发表时间：
2016-01-01
影响因子：
9.8
作者：
Birmingham, Daniel J.;Bitter, Joshua E.;Hebert, Lee A.
通讯作者：
Hebert, Lee A.