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Casanova Lab Profile picture
@casanova_lab
Jan 29, 2020 • 3 tweets • 3 min read • Read on X
Death from #CMV primary infection in humans without any medical history was unexplained and the role of human inducible nitric oxide synthase (#NOS2) was unknown.
Our study reported in @NEJM today provided the first answer to both questions: nejm.org/doi/full/10.10… @ALNeehus @BigioBenedetta @BustamanteJaci1 @LaurentAbel4 @BoissonDupuis @BeziatV
It also connected 2 old friends of the lab, Davood Mansouri in Tehran (who attended a patient who died of #CMV at age 54) & Carl Nathan in NY (who discovered #NOS2 & characterized its function in mice). We found that the patient died of CMV because of AR complete NOS2 deficiency.

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More from @casanova_lab

Casanova Lab Profile picture
Jan 4
1/ 📢 📰 In @JExpMed, we report that about 10% of children with life-threatening #COVID19 harbor auto-antibodies to type I IFNs. ()rupress.org/jem/article/22…
2/ Since first being discovered in a patient with severe VZV infection by Ion Gresser in 1984, these auto-Abs have been thought to be silent 🔇()jstor.org/stable/30134062
3/ It wasn’t until 2020, that we uncovered that neutralizing auto-Abs to type I IFNs actually account for at least 10% of critical cases of #COVID19. The prevalence of these auto-Abs increases in the elderly 👵. ()science.org/doi/10.1126/sc…
Read 12 tweets
Casanova Lab Profile picture
Nov 8, 2023
1/ We are excited to report in @Nature the discovery that human inborn errors of the alternative NF-κB pathway-dependent immunity underlie the development of auto-Abs neutralizing type I IFNs ().rdcu.be/dqBBU
2/ Auto-Abs neutralizing type I IFNs are present in the general population, with a prevalence that sharply increases over 70 years old, reaching 4-8% ().science.org/doi/10.1126/sc…
3/ Auto-Abs to type I IFNs underlie various viral diseases, including about 15% of cases of critical COVID-19, 5% of cases of critical influenza, and 40% of cases of West Nile virus encephalitis ().rupress.org/jem/article/22…
Read 16 tweets
Casanova Lab Profile picture
Apr 22, 2023
1/ We are happy to share our report of inherited RIPK3 deficiency in a child with HSV-1 encephalitis (HSE) in @SciImmunology (doi.org/10.1126/sciimm…­­­­­). HUGE thanks to all collaborators (list below)!
2/ HSV-1 is a ubiquitous virus that infects over 80% of the global population. HSE is perhaps the most common sporadic life-threatening encephalitis in the world.
3/ Since 2006, we and others have discovered 14 inborn errors of immunity underlying HSE, most of which disrupt type I IFN immunity in the brain (doi.org/10.1126/scienc…; doi.org/10.1126/sciimm…). Image
Read 12 tweets
Casanova Lab Profile picture
Feb 10, 2023
1/ We are excited to share exciting news about human IL-23 in #ScienceImmunology (science.org/doi/10.1126/sc…).
2/ The early 2000s discovery of IL-23 and IL-23R was associated with the characterization of TH17 cells as distinct T-cell lineage, different from TH1 / TH2 cells (nature.com/articles/natur…).
3/ In this paradigm, IL-12 is the IFN--inducing signature cytokine, whereas IL-23 is the IL-17-inducing signature cytokine (nature.com/articles/nm.38…).
Read 15 tweets
Casanova Lab Profile picture
Feb 2, 2023
1/ We are excited to share some news about human IRF1, which surprisingly turns out to be the key transcription factor downstream from IFN-gamma and STAT1 in macrophages (sciencedirect.com/science/articl…).
2/ IRF1 was discovered in 1988 by Tada Taniguchi (tinyurl.com/mr48xn5e). In 1993, his team also reported IRF1-deficient mice (tinyurl.com/387mwvup). Both studies were published in @CellCellPress.
3/ IRF1 was characterized as a transcription factor essential for the development of NK and CD8 TR cells, as well as the action of both type I and type II IFNs. It was also the first member of the large family of IRFs (tinyurl.com/y8ntvvsf).
Read 13 tweets
Casanova Lab Profile picture
Dec 20, 2022
1/ Together with the COVID Human Genetics Effort, we are happy to report our finding of inborn errors of the OAS-RNase L pathway in children with MIS-C #Misc #Pims in @ScienceMagazine (science.org/doi/10.1126/sc…)
2/ Multisystem inflammatory syndrome of children (MIS-C) is characterized by a massive inflammation about 4 weeks post benign #COVID19 upon infection by #SARSCoV2, with life-threatening cardio-vascular manifestations (nejm.org/doi/10.1056/NE…; link.springer.com/article/10.100…)
3/ A specific feature of MIS-C is the massive expansion of Vbeta21.3 CD4 and CD8 T cells in most patients (science.org/doi/10.1126/sc…, doi.org/10.1016/j.immu…, nature.com/articles/s4159…, jci.org/articles/view/…, doi.org/10.1084/jem.20…)
Read 20 tweets

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