Persistent Bacteriuria and Antibodies Recognizing Curli/eDNA Complexes From Escherichia coli Are Linked to Flares in Systemic Lupus Erythematosus.
Persistent Bacteriuria and Antibodies Recognizing Curli/eDNA Complexes From Escherichia coli Are Linked to Flares in Systemic Lupus Erythematosus.
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DOI：
10.1002/art.41400
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Caricchio R
中科院分区：
文献类型：
--
作者：
Pachucki RJ;Corradetti C;Kohler L;Ghadiali J;Gallo PM;Nicastro L;Tursi SA;Gallucci S;Tükel Ç;Caricchio R
感染有助于狼疮的发病率和死亡率，在这里，我们问他们是否也可能在其发病机制中发挥作用。肾盂肾炎大肠大肠杆菌（UPEC）引起尿路感染（UTI）并形成生物膜，即由淀粉样蛋白（如curli）加强的多细胞细菌群落。我们以前报道过curli与DNA天然形成复合物（curli/eDNA），这些复合物在小鼠模型中诱导狼疮疾病的标志。我们调查了96例符合至少4项SLICC标准的SLE患者。我们测试了IgG和伊加亚类的抗卷曲/eDNA复合物抗体的存在。结果与54名年龄、性别和种族匹配的健康对照组进行比较。然后，我们将抗curli/eDNA抗体水平与临床参数、狼疮疾病状态和菌尿频率相关联。我们在SLE和对照血浆中发现了抗curli/eDNA抗体，其水平与狼疮患者的无症状持续性菌尿和疾病发作相关。持续性菌尿含有产生卷曲的UPEC，并与炎症表型相关。最后，curli/eDNA复合物在结合自身抗体中与狼疮自身抗原如dsDNA交叉反应。我们认为尿路感染或持续性菌尿是狼疮及其耀斑的环境触发因素。针对curli/eDNA的抗体可以作为狼疮患者全身暴露于细菌产物的标志。
Infections contribute to morbidity and mortality in lupus, here we asked if they might also play a role in its pathogenesis. Uropathogenic E. coli (UPEC) cause urinary tract infections (UTIs) and form biofilms, multicellular communities of bacteria that are strengthen by amyloids such as curli. We previously reported that curli naturally form complexes with DNA (curli/eDNA) and these complexes induce hallmarks of lupus disease in mouse models. We investigated 96 SLE patients who met at least 4 SLICC criteria. We tested the presence of anti-curli/eDNA complex antibodies for both IgG and IgA subclasses. Results were compared to 54 age, sex and race matched healthy controls. We then correlated the levels of anti-curli/eDNA antibodies with clinical parameters, lupus disease status and frequency of bacteriuria. We found anti-curli/eDNA antibodies in SLE and controls plasma, and their levels correlated with asymptomatic persistent bacteriuria and disease flares in lupus patients. Persistent bacteriuria contained curli-producing UPEC and associated with an inflammatory phenotype. Finally, curli/eDNA complexes cross-reacted with lupus autoantigens such as dsDNA in binding autoantibodies. We propose that UTIs or persistent bacteriuria are environmental triggers of lupus and its flares. Antibodies against curli/eDNA could serve as a sign of systemic exposure to bacterial products in lupus.
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影响因子：
3.7
作者：
Shi L;Zhang Z;Yu AM;Wang W;Wei Z;Akhter E;Maurer K;Costa Reis P;Song L;Petri M;Sullivan KE
通讯作者：
Sullivan KE
影响因子：
2.6
作者：
Jog NR;Blanco I;Lee I;Putterman C;Caricchio R
通讯作者：
Caricchio R
影响因子：
2.6
作者：
Pisetsky, D. S.;Vrabie, I. A.
通讯作者：
Vrabie, I. A.
影响因子：
2.1
作者：
Anjo, C.;Mascaro, J-M, Jr.;Cervera, R.
通讯作者：
Cervera, R.
影响因子：
27.4
作者：
Bruce IN;O'Keeffe AG;Farewell V;Hanly JG;Manzi S;Su L;Gladman DD;Bae SC;Sanchez-Guerrero J;Romero-Diaz J;Gordon C;Wallace DJ;Clarke AE;Bernatsky S;Ginzler EM;Isenberg DA;Rahman A;Merrill JT;Alarcón GS;Fessler BJ;Fortin PR;Petri M;Steinsson K;Dooley MA;Khamashta MA;Ramsey-Goldman R;Zoma AA;Sturfelt GK;Nived O;Aranow C;Mackay M;Ramos-Casals M;van Vollenhoven RF;Kalunian KC;Ruiz-Irastorza G;Lim S;Kamen DL;Peschken CA;Inanc M;Urowitz MB
通讯作者：
Urowitz MB