米エール大学の岩崎明子教授がリング教授のラボと出した、新型コロナウイルス感染症で出る自己抗体についての論文のまとめ
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medRxiv
@medrxivpreprint
Diverse Functional Autoantibodies in Patients with COVID-19 medrxiv.org/cgi/content/sh… #medRxiv
2020-12-12 04:42:51
Prof. Akiko Iwasaki
@VirusesImmunity
We study antiviral immunity and viral disease pathogenesis. #COVID19 #longCOVID #vaccines @HHMINEWS @YaleIBIO @YaleMed @YaleCII President of @ImmunologyAAI
Prof. Akiko Iwasaki
@VirusesImmunity
New exciting collaboration work with @Aaronmring lab reveals diverse and functional autoantibodies in #COVID patients. Our findings provide clues for why COVID affects many organs, induce range of symptoms that are long lasting. Thread (1/n) medrxiv.org/content/10.110…
2020-12-12 10:46:19
Aaron Ring
@aaronmring
Associate Professor at @FredHutch Studying #cytokines, (auto)antibodies, and #cancerimmunotherapy Founder: @SimchaTx, @Seranova, & Stipple Bio
Prof. Akiko Iwasaki
@VirusesImmunity
How do we look for autoantibodies against a wide range of self antigens? The @aaronmring lab developed a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) against 2,770 extracellular and secreted proteins "exoproteome" 💪🏼 (2/n) pic.twitter.com/C1AKXJ7F90
2020-12-12 10:46:20
拡大
Prof. Akiko Iwasaki
@VirusesImmunity
A large fraction of #COVID patients had autoantibodies to multiple self antigens. The more severe the disease, more autoantibodies they had.(3/n) pic.twitter.com/M8PdSmUx8b
2020-12-12 10:46:22
拡大
Prof. Akiko Iwasaki
@VirusesImmunity
So what are the targets of these autoantibodies? It turns out to be many. Some antibodies bound to interferons, chemokine and cytokines, while others bound to proteins expressed on the surface of immune and non-immune cells. (4/n) pic.twitter.com/5dboOeOWke
2020-12-12 10:46:23
拡大
Prof. Akiko Iwasaki
@VirusesImmunity
Here are the autoantigens that are detected by antibodies in COVID patients. Columns represent patients. Rows are antigens. Notice the frequency of anti-interferon antibodies in severe COVID patients! Very reminiscent of this study👇🏽 (5/n) science.sciencemag.org/content/370/65… pic.twitter.com/uwrkXHtjqH
2020-12-12 10:46:25
拡大
Prof. Akiko Iwasaki
@VirusesImmunity
These autoantibodies to IFN-I are likely functional - people who have them were unable to control viral load, compared to those without - matched for comparable average age, sex, and disease severity. (6/n) pic.twitter.com/XhUyClCPD1
2020-12-12 10:46:26
拡大
Prof. Akiko Iwasaki
@VirusesImmunity
In addition to IFN-I, there were many other immune proteins that become target of antibody attack. IL-1α/β, IL-6, GM-CSF, IL-18Rβ, and Leptin (LEP). Chemokine autoantibody targets included CXCL1, CXCL7, CCL2, CCL15, CCL16, and the chemokine decoy receptor ACKR1. (7/n)
2020-12-12 10:46:27
Prof. Akiko Iwasaki
@VirusesImmunity
Surface autoantigens on immune cells also found; NKG2D ligands (RAET1E/L, ULBP1/2), NK cell receptors NKG2A/C/E (KLRC1/2/3), B cell-expressed proteins (CD38, FCMR, FCRL3, CXCR5), T cell expressed proteins (CD3E, CXCR3, CCR4), and myeloid expressed proteins (CCR2, CD300E).(8/n)
2020-12-12 10:46:28
Prof. Akiko Iwasaki
@VirusesImmunity
These Abs appear to be functional in vivo. People who had anti-B cell antibodies had very low number of circulating B cells and very low IgM response against RBD. (9/n) pic.twitter.com/zqDzHdkItD
2020-12-12 10:46:29
拡大
Prof. Akiko Iwasaki
@VirusesImmunity
One patient with autoantibodies against CD3E (a component of the T cell receptor complex) had intact B and NK cell compartments but dramatically reduced levels of CD4 T cells, CD8 T cells, and NKT cells in the blood. (10/n) pic.twitter.com/sLMaRO6g1l
2020-12-12 10:46:30
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Prof. Akiko Iwasaki
@VirusesImmunity
Another way we validated the function of the autoantibodies is through the use of mouse model. Anti-IFNAR or anti-IL-18 Ab treatment of mice rendered them more susceptible to disease and death after #SARSCoV2 challenge. (11/n) pic.twitter.com/2NSyUDsFtC
2020-12-12 10:46:33
拡大
Prof. Akiko Iwasaki
@VirusesImmunity
In addition to immune-related antigens, we also found antibodies to various tissue-specific antigens in organs like the central nervous system, vascular, connective tissues, liver, GI tract..etc. Such antibodies could drive damage in target tissues. (12/n) pic.twitter.com/wmyhzk33pn
2020-12-12 10:46:35
拡大
Prof. Akiko Iwasaki
@VirusesImmunity
Some of the autoantibodies were found from the very beginning of analysis, while others were induced during the course of study. Others declined in their levels over time. (13/n) pic.twitter.com/iVBjMitzzb
2020-12-12 10:46:36
拡大
Toyo@呼吸器内科専門医
@toyosh
ついに出ましたね。プレプリントですが、コロナ患者に様々な病的意義を持つ自己抗体の存在が証明されました。詳しく読もう。 twitter.com/virusesimmunit…
2020-12-12 23:57:44
Toyo@呼吸器内科専門医
@toyosh
今読み始めてますが、これは凄い。自分も４月には予想していた重症化機序ですが、結局それを実際に大規模に、網羅的に、そして機能的証明もとって論文化するアメリカの科学力、組織力、共同研究力に打ちのめされていまいます。どうやってこの世界で戦っていくのか。これからの自分の課題です。
2020-12-13 00:22:18
入瀬 美十
@Bijoux01
@VirusesImmunity @Eric_Y_Wang @tianyangmao @sneakyvirus1 凄いです！感動しました！！ツイートありがとうございました！
2020-12-13 00:16:18
Toyo@呼吸器内科専門医
@toyosh
詳細に読んで、この研究での一つの課題としては、細胞外蛋白質2770種類のスクリーニングであるので、僕の認識が正しければ、重症肺障害機序として予想しているMDA5抗体やARS抗体はこの系では検出されません。細胞内抗原に対する自己抗体スクリーニングも次の課題かと考えました。 twitter.com/toyosh/status/…
2020-12-14 11:01:20