Jamaly Simin, Tsokos Maria G, Bhargava Rhea, Brook Olga R, Hecht Jonathan L, Abdi Reza, Moulton Vaishali R, Satyam Abhigyan, Tsokos George C
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Department of Medical Biology, Faculty of Health Science, UiT Arctic University of Norway, N-9037 Tromsø, Norway.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Clin Immunol. 2021 Aug;229:108795. doi: 10.1016/j.clim.2021.108795. Epub 2021 Jul 10.
Acute and chronic kidney failure is common in hospitalized patients with COVID-19, yet the mechanism of injury and predisposing factors remain poorly understood. We investigated the role of complement activation by determining the levels of deposited complement components (C1q, C3, FH, C5b-9) and immunoglobulin along with the expression levels of the injury-associated molecules spleen tyrosine kinase (Syk), mucin-1 (MUC1) and calcium/calmodulin-dependent protein kinase IV (CaMK4) in the kidney tissues of people who succumbed to COVID-19. We report increased deposition of C1q, C3, C5b-9, total immunoglobulin, and high expression levels of Syk, MUC1 and CaMK4 in the kidneys of COVID-19 patients. Our study provides strong rationale for the expansion of trials involving the use of inhibitors of these molecules, in particular C1q, C3, Syk, MUC1 and CaMK4 to treat patients with COVID-19.
急性和慢性肾衰竭在新冠肺炎住院患者中很常见，但损伤机制和易感因素仍知之甚少。我们通过测定死亡的新冠肺炎患者肾组织中沉积的补体成分（C1q、C3、FH、C5b-9）和免疫球蛋白水平以及损伤相关分子脾酪氨酸激酶（Syk）、粘蛋白-1（MUC1）和钙/钙调蛋白依赖性蛋白激酶IV（CaMK4）的表达水平，研究了补体激活的作用。我们报告称，新冠肺炎患者肾脏中C1q、C3、C5b-9、总免疫球蛋白沉积增加，Syk、MUC1和CaMK4表达水平升高。我们的研究为扩大涉及使用这些分子抑制剂（特别是C1q、C3、Syk、MUC1和CaMK4）治疗新冠肺炎患者的试验提供了有力依据。
