High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis.
High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis.
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高全身 I 型干扰素活性与活动性 III/IV 类狼疮肾炎相关。
DOI：
10.3899/jrheum.210391
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Niewold TB
中科院分区：
文献类型：
--
作者：
Iwamoto T;Dorschner JM;Selvaraj S;Mezzano V;Jensen MA;Vsetecka D;Amin S;Makol A;Osborn T;Moder K;Chowdhary VR;Izmirly P;Belmont HM;Clancy RM;Buyon JP;Wu M;Loomis CA;Niewold TB
以往的研究表明，高血清I型干扰素（IFN）和狼疮性肾炎（LN）之间的联系。我们确定了血清IFN活性是否与LN亚型相关，并研究了肾组织和细胞以了解IFN在LN中的影响。对221例系统性红斑狼疮（SLE）患者进行了研究。采用WISH生物测定法测定血清干扰素活性。在肾组织中使用mRNA原位杂交来测量代表性IFN诱导的基因、干扰素诱导的三肽重复序列-1（IFIT 1）蛋白和浆细胞样树突状细胞（pDC）标记基因C型凝集素结构域家族-4成员C（CLEC 4C或BDCA 2）的表达。通过实时PCR测量足细胞系基因表达。与低IFN水平患者相比，高IFN水平患者的III/IV类LN患病率显著增加（OR=5.48，p=4.0×10−7）。在多变量回归模型中，I型IFN是比补体C3或抗dsDNA抗体更强的III/IV类LN的预测因子，并且可以解释这些变量与LN的关联。IFIT 1的表达增加，在所有类型的LN，但最活跃的III/IV类LN肾的肾小球区域。IFIT 1表达与pDC没有紧密共定位。IFN直接激活足细胞系诱导趋化因子和促凋亡分子。系统性高IFN参与了重症LN的发病机制。我们没有发现pDC与IFN信号在肾组织中的共定位，而是在肾小球区域观察到最大强度的IFN信号，这可能表明IFN的血液来源。
Previous studies suggest a link between high serum type I interferon (IFN) and lupus nephritis (LN). We determined whether serum IFN activity is associated with subtypes of LN and studied renal tissues and cells to understand the impact of IFN in LN. 221 systemic lupus erythematosus (SLE) patients were studied. Serum IFN activity was measured by WISH bioassay. mRNA in-situ hybridization was used in renal tissue to measure expression of the representative IFN-induced gene, interferon-induced protein with tetratricopeptide repeats-1 (IFIT1), and the plasmacytoid dendritic cell (pDC) marker gene C-type lectin domain family-4 member C (CLEC4C or BDCA2). Podocyte cell line gene expression was measured by real-time PCR. Class III/IV LN prevalence was significantly increased in patients with high serum IFN compared with those with low IFN (OR=5.48, p=4.0×10−7). In multivariate regression models, type I IFN was a stronger predictor of class III/IV LN than complement C3 or anti-dsDNA antibody, and could account for the association of these variables with LN. IFIT1 expression was increased in all classes of LN, but most in the glomerular areas of active class III/IV LN kidneys. IFIT1 expression was not closely co-localized with pDCs. IFN directly activated podocyte cell lines to induce chemokines and proapoptotic molecules. Systemic high IFN is involved in the pathogenesis of severe LN. We do not find co-localization of pDCs with IFN signature in renal tissue, and instead observe the greatest intensity of IFN signature in glomerular areas, which could suggest a blood source of IFN.
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影响因子：
5.5
作者：
Bastian, H. M.;Alarcon, G. S.;Reveille, J. D.
通讯作者：
Reveille, J. D.
影响因子：
5.5
作者：
Croca, Sara C.;Rodrigues, Teresa;Isenberg, David A.
通讯作者：
Isenberg, David A.
影响因子：
27.4
作者：
Niewold TB;Kelly JA;Kariuki SN;Franek BS;Kumar AA;Kaufman KM;Thomas K;Walker D;Kamp S;Frost JM;Wong AK;Merrill JT;Alarcón-Riquelme ME;Tikly M;Ramsey-Goldman R;Reveille JD;Petri MA;Edberg JC;Kimberly RP;Alarcón GS;Kamen DL;Gilkeson GS;Vyse TJ;James JA;Gaffney PM;Moser KL;Crow MK;Harley JB
通讯作者：
Harley JB
影响因子：
4.7
作者：
Mina R;Abulaban K;Klein-Gitelman MS;Eberhard BA;Ardoin SP;Singer N;Onel K;Tucker L;O'neil K;Wright T;Brooks E;Rouster-Stevens K;Jung L;Imundo L;Rovin B;Witte D;Ying J;Brunner HI
通讯作者：
Brunner HI
DOI：
10.1016/j.trsl.2014.10.005
发表时间：
2015-02
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Crow MK;Olferiev M;Kirou KA
通讯作者：
Kirou KA