Fu Wenyan, Liu Yu, Liu Fangjie, Liu Chenghua, Li Jingjing, Niu Jiali, Han Peng, Xu Dan, Hou Jiaojiao, Ma Yuanfang, Feng Jiannan, Li Zhanguo, Mu Rong, Yang Guang
Beijing Institute of Pharmacology and Toxicology, Beijing, China.
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing, China.
Front Immunol. 2021 Mar 25;12:656090. doi: 10.3389/fimmu.2021.656090. eCollection 2021.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple autoantibody production and often affects the kidneys, known as lupus nephritis. However, the mechanism underlying lupus nephritis development is unclear. Biofilms that protect bacteria from stress are ubiquitous in almost every environment. Here, we identified that a conserved peptide (HU1) derived from DNABII proteins, one of major bacterial biofilm components, was specifically recognized by sera from about 47% patients with SLE. Moreover, the serum anti-HU1 levels showed a significant positive correlation with lupus nephritis occurrence. Presence of antibodies against HU1 in pristane-induced mice aggravated lupus nephritis, although these antibodies also attenuated bacterial biofilm formation. We further identified that antibodies against HU1 cross-recognized protein disulfide isomerase (P4HB) located on the renal cell surface and inhibited the activities of this enzyme. Our findings reveal a novel mechanism underlying the development of lupus nephritis triggered by bacterial biofilms.
系统性红斑狼疮（SLE）是一种产生多种自身抗体的全身性自身免疫性疾病，常累及肾脏，称为狼疮性肾炎。然而，狼疮性肾炎发展的潜在机制尚不清楚。保护细菌免受应激的生物膜几乎在每个环境中都普遍存在。在此，我们发现一种源自主要细菌生物膜成分之一DNABII蛋白的保守肽（HU1）能被约47%的SLE患者血清特异性识别。此外，血清抗HU1水平与狼疮性肾炎的发生呈显著正相关。在 pristane 诱导的小鼠中，抗HU1抗体的存在加重了狼疮性肾炎，尽管这些抗体也减弱了细菌生物膜的形成。我们进一步发现，抗HU1抗体可交叉识别位于肾细胞表面的蛋白二硫键异构酶（P4HB）并抑制该酶的活性。我们的研究结果揭示了细菌生物膜引发狼疮性肾炎发展的一种新机制。
