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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
Sep 25, 2024
1/ We are excited to share our report in #JEM that about 10% of severe tick-borne encephalitis (TBE) cases, triggered by the TBE virus (TBEV), are due to pre-existing auto-Abs neutralizing type I IFNs (). doi.org/10.1084/jem.20…
Image
2/ TBEV, an orthoflavivirus transmitted by infected ticks, is endemic in Europe and Asia. Infection is typically silent or benign but can underlie encephalitis in rare cases. The incidence of TBE is rising globally, with about 0.9 cases per 100,000 individuals reported in 2020. Image
3/ We previously showed that auto-Abs to type I IFNs underlie about 15% of cases of critical COVID-19, 5% of cases of critical influenza, and 3 out of 8 rare adverse reactions to the Yellow Fever virus (YFV) live-attenuated vaccine ().doi.org/10.1084/jem.20…
Read 14 tweets
Casanova Lab Profile picture
Jan 4, 2024
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

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