Evidence of a Sjögren's disease-like phenotype following COVID-19 in mice and humans.
Evidence of a Sjögren's disease-like phenotype following COVID-19 in mice and humans.
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DOI：
10.1172/jci.insight.166540
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发表时间：
2023-12-22
期刊：
影响因子：
8
通讯作者：
Nguyen, Cuong Q.
中科院分区：
文献类型：
--
作者：
Shen, Yiran;Voigt, Alexandria;Goranova, Laura;Abed, Mehdi;Kleiner, David E.;Maldonado, Jose O.;Beach, Margaret;Pelayo, Eileen;Chiorini, John A.;Craft, William F.;Ostrov, David A.;Ramiya, Vijay;Sukumaran, Sukesh;Brown, Ashley N.;Hanrahan, Kaley C.;Tuanyok, Apichai;Warner, Blake M.;Nguyen, Cuong Q.
干燥病（SjD）是一种全身性自身免疫性疾病，其特征是泪腺和唾液腺（SG）的淋巴细胞炎症、眼干和口干以及全身症状。SARS-CoV-2可能引发自身免疫性疾病的发展或进展。为了验证这一点，我们使用了SARS-CoV-2感染的小鼠模型和恢复期患者的血液和SG，以了解感染后SjD样自身免疫的发展。首先，SARS-CoV-2感染的人血管紧张素转换酶2（ACE 2）转基因小鼠表现出唾液分泌减少，抗核抗体（ANA）升高，泪腺和SG淋巴细胞浸润。来自COVID-19血清患者的血清显示ANA增加（即，抗SSA [干燥综合征相关抗原A]/抗Ro 52和抗SS B [SS-抗原B]/抗La）。与女性患者相比，男性患者抗SSA升高，女性患者表现出不同的ANA模式。恢复期COVID-19患者的SG活检在显微镜下与SjD SG相似，6例患者中有4例出现局灶性淋巴细胞浸润，6例患者中有2例病灶评分至少为2。最后，恢复患者产生的单克隆抗体阻断ACE 2/刺钉相互作用，并与核抗原交叉反应。我们的研究表明SARS-CoV-2和SjD之间存在直接关联。受SjD影响的SG的标志性特征在组织学上与恢复期COVID-19患者无法区分。结果表明，SARS-CoV-2可能是SjD的环境触发因素。
Sjögren’s Disease (SjD) is a systemic autoimmune disease characterized by lymphocytic inflammation of the lacrimal and salivary glands (SG), dry eyes and mouth, and systemic symptoms. SARS-CoV-2 may trigger the development or progression of autoimmune diseases. To test this, we used a mouse model of SARS-CoV-2 infection and convalescent patients’ blood and SG in order to understand the development of SjD-like autoimmunity after infection. First, SARS-CoV-2–infected human angiotensin-converting enzyme 2 (ACE2) transgenic mice exhibited decreased salivation, elevated antinuclear antibodies (ANA), and lymphocytic infiltration in the lacrimal and SG. The sera from patients with COVID-19 sera showed increased ANA (i.e., anti-SSA [Sjögren’s-syndrome-related antigen A]/anti-Ro52 and anti-SSB [SS-antigen B]/anti-La). Male patients showed elevated anti-SSA compared with female patients, and female patients exhibited diverse ANA patterns. SG biopsies from convalescent COVID-19 patients were microscopically similar to SjD SG with focal lymphocytic infiltrates in 4 of 6 patients and 2 of 6 patients exhibiting focus scores of at least 2. Lastly, monoclonal antibodies produced in recovered patients blocked ACE2/spike interaction and cross-reacted with nuclear antigens. Our study shows a direct association between SARS-CoV-2 and SjD. Hallmark features of SjD-affected SGs were histologically indistinguishable from convalescent COVID-19 patients. The results implicate that SARS-CoV-2 could be an environmental trigger for SjD.
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影响因子：
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DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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影响因子：
6.4
作者：
Nguyen, Cuong Q.;Peck, Ammon B.
通讯作者：
Peck, Ammon B.