The mechanism of self-recognition of the autoantigen TROVE2, a common biomarker in autoimmune diseases, has been studied with a quartz crystal microbalance with dissipation monitoring (QCM-D) and dual polarization interferometry (DPI). The complementarity and remarkable analytical features of both techniques has allowed new insights into the onset of systemic lupus erythematosus (SLE) to be achieved at the molecular level. The in vitro study for SLE patients and healthy subjects suggests that anti-TROVE2 autoantibodies may undergo an antibody bipolar bridging. An epitope-paratope-specific binding initially occurs to activate a hidden Fc receptor in the TROVE2 tertiary structure. This bipolar mechanism may contribute to the pathogenic accumulation of anti-TROVE2 autoantibody immune complex in autoimmune disease. Furthermore, the specific calcium-dependent protein-protein bridges point out at how the TRIM21/TROVE2 association might occur, suggesting that the TROVE2 protein could stimulate the intracellular immune signaling via the TRIM21 PRY-SPRY domain. These findings may help to better understand the origins of the specificity and affinity of TROVE2 interactions, which might play a key role in the SLE pathogenesis. This manuscript gives one of the first practical applications of two novel functions (−df/dD and Δh/molec) for the analysis of the data provided by QCM-D and DPI. In addition, it is the first time that QCM-D has been used for mapping hidden Fc receptors as well as linear epitopes in a protein tertiary structure.

中文翻译：

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通过QCM-D和DPI结合确定TROVE2复合物在系统性红斑狼疮的发病和发病机制中的作用的新结构见解

自身抗原TROVE2（一种自身免疫疾病中的常见生物标记物）的自我识别机制已通过具有耗散监测（QCM-D）和双极化干涉仪（DPI）的石英晶体微量天平进行了研究。两种技术的互补性和非凡的分析特性使我们能够在分子水平上全面了解系统性红斑狼疮（SLE）的发作。针对SLE患者和健康受试者的体外研究表明，抗TROVE2自身抗体可能会经历抗体双极性桥接。最初发生表位-对位特异性结合，以激活TROVE2三级结构中的隐藏Fc受体。这种双极性机制可能有助于自身免疫性疾病中抗TROVE2自身抗体免疫复合物的致病性积累。此外，特定的钙依赖性蛋白-蛋白桥指出了TRIM21 / TROVE2缔合可能如何发生，这表明TROVE2蛋白可以通过TRIM21 PRY-SPRY结构域刺激细胞内免疫信号传导。这些发现可能有助于更好地了解TROVE2相互作用的特异性和亲和力的起源，这可能在SLE发病机理中起关键作用。该手稿给出了两种新颖功能（-d 这可能在SLE发病机理中起关键作用。该手稿给出了两种新颖功能（-d 这可能在SLE发病机理中起关键作用。该手稿给出了两种新颖功能（-d˚F / d d和Δ ħ / molec），用于通过QCM-d和DPI提供的数据的分析。此外，这是第一次将QCM-D用于在蛋白质三级结构中定位隐藏的Fc受体以及线性表位。