驚愕
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
— Prof. Akiko Iwasaki (@VirusesImmunity) December 12, 2020
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
— Prof. Akiko Iwasaki (@VirusesImmunity) December 12, 2020
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
— Prof. Akiko Iwasaki (@VirusesImmunity) December 12, 2020
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)
— Prof. Akiko Iwasaki (@VirusesImmunity) December 12, 2020
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
— Prof. Akiko Iwasaki (@VirusesImmunity) December 12, 2020
CD4 T cells, CD8 T cells, and NKT cells in the blood. (10/n) pic.twitter.com/sLMaRO6g1l
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
— Prof. Akiko Iwasaki (@VirusesImmunity) December 12, 2020
There are many unanswered questions. How long do these autoantibodies last? What damage do they cause? How are they induced? Do they occur in #LongCovid?
— Prof. Akiko Iwasaki (@VirusesImmunity) December 12, 2020
Finally, this was a heroic effort by many, led by @Eric_Y_Wang @tianyangmao @sneakyvirus1 Yile Dai and Yale IMPACT team 👏🏼
