DataSheet_1_A Novel Autoantibody Induced by Bacterial Biofilm Conserved Components Aggravates Lupus Nephritis.pdf

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（Systemic lupus erythematosus, SLE）是一种全身性自身免疫性疾病，以产生多种自身抗体为主要特征，常累及肾脏，此时称为狼疮性肾炎。然而，狼疮性肾炎的发病机制目前尚未阐明。可帮助细菌抵御外界应激的生物被膜（biofilm）几乎遍布所有自然环境。本研究发现，源自细菌生物被膜主要组分之一DNABII蛋白的保守肽段HU1，可被约47%的SLE患者血清特异性识别。此外，血清抗HU1抗体水平与狼疮性肾炎的发生呈显著正相关。在植烷诱导的狼疮模型小鼠体内，抗HU1抗体可加重狼疮性肾炎的病情，尽管此类抗体同时可抑制细菌生物被膜的形成。本研究进一步证实，抗HU1抗体可交叉识别肾细胞表面的蛋白二硫键异构酶（protein disulfide isomerase, P4HB）并抑制该酶的催化活性。本研究结果揭示了一条由细菌生物被膜介导的狼疮性肾炎发病新机制。