兒童多系統炎症症候群患者自身炎症和抗體反應圖譜的揭示
作者:
小柯機器人發布時間:2020/9/15 21:48:55
美國西奈山伊坎醫學院Dusan Bogunovic及其研究團隊揭示了兒童多系統炎症症候群(MIS-C) 患者全身炎症和抗體反應的圖譜。 這一研究成果在線發表在2020年9月14日的《細胞》上。
研究人員揭示了9例MIS-C患者的免疫情況。所有MIS-C患者都有先前暴露於嚴重急性呼吸系統綜合症冠狀病毒2(SARS-CoV-2)的經歷,具有完整中和能力的抗體應答。細胞因子譜系分析表明患者具有炎症反應(IL-18和IL-6)、淋巴細胞和髓細胞趨化性、激活(CCL3、CCL4和CDCP1)和黏膜免疫失調(IL-17A、CCL20、CCL28)等信號增強的特徵。
外周血免疫分型表明非經典單核細胞以及NK和T淋巴細胞亞群的減少,這表明其滲入了受影響的組織。最後,通過分析MIS-C患者的血漿自身抗原反應,研究人員揭示了已知疾病相關的自身抗體(anti-La)和識別內皮、胃腸道和免疫細胞抗原的新型候選抗體。所有患者均接受抗IL6R抗體和/或IVIG的治療,從而可快速治癒疾病。
研究人員表示,起初人們認為兒童可以免受SARS-CoV-2引起的疾病。然而,在該疾病流行一個月後,出現了一種新型的MIS-C。
附:英文原文
Title: Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)
Author: Conor Gruber, Roosheel S. Patel, Rebecca Trachtman, Lauren Lepow, Fatima Amanat, Florian Krammer, Karen M. Wilson, Kenan Onel, Daniel Geanon, Kevin Tuballes, Manishkumar Patel, Konstantinos Mouskas, Timothy ODonnell, Elliot Merritt, Nicole Simons, Vanessa Barcessat, Diane M. Del Valle, Samantha Udondem, Gurpawan Kang, Sandeep Gangadharan, George Ofori-Amanfo, Uri Laserson, Adeeb Rahman, Seunghee Kim-Schulze, Alexander Charney, Sacha Gnjatic, Bruce D. Gelb, Miriam Merad, Dusan Bogunovic
Issue&Volume: 2020-09-14
Abstract: Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK- and T- lymphocytes, suggesting extravasation to affected tissues. Finally, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti-IL6R antibody and/or IVIG, which led to rapid disease resolution.
DOI: 10.1016/j.cell.2020.09.034
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31231-9
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