Papasavvas Emmanouil, Lu Lily, Fair Matthew, Oliva Isabela, Cassel Joel, Majumdar Sonali, Mounzer Karam, Kostman Jay R, Tebas Pablo, Bar-Or Amit, Muthumani Kar, Montaner Luis J
bioRxiv. 2024 May 5:2024.05.05.591636. doi: 10.1101/2024.05.05.591636.
Type I interferons (IFNs) play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-β antibodies (Abs) from peripheral blood mononuclear cells of individuals treated with IFN-α or IFN-β, harboring confirmed neutralizing Abs. Clones AH07856 and AH07857 were identified as neutralizing anti-IFN-α-specific with inhibition against IFN-α2a, -α2b, and -αK subtypes. Clones AH07859 and AH07866 were identified as neutralizing anti-IFN-β1a-specific signaling, and able to block Lipopolysaccharide or S100 calcium binding protein A14-induced IFN-β signaling effects. Cloned Abs bind rhesus but not murine IFNs. The specificity of inhibition between IFN-α and IFN-β suggests potential for diverse research and clinical applications.
I型干扰素（IFNs）在免疫反应调节中起关键作用，但失调与多种疾病有关。因此，开发有助于理解其作用机制并能制定更有效抗干扰素治疗策略的工具至关重要。在本研究中，我们从接受过α干扰素或β干扰素治疗且携带已确认中和抗体的个体外周血单个核细胞中分离、克隆并鉴定了抗α干扰素和抗β干扰素抗体（Abs）。克隆株AH07856和AH07857被鉴定为具有中和作用的抗α干扰素特异性抗体，可抑制α2a、α2b和αK亚型的α干扰素。克隆株AH07859和AH07866被鉴定为具有中和作用的抗β1a干扰素特异性信号抗体，能够阻断脂多糖或S100钙结合蛋白A14诱导的β干扰素信号效应。克隆的抗体可结合恒河猴干扰素，但不结合鼠干扰素。α干扰素和β干扰素之间抑制作用的特异性表明其在多种研究和临床应用中具有潜力。
