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…
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.

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

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…

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.

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…).

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.

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…)

1/ We are happy to share with you our paper in @JExpMed reporting auto-Abs to type I IFNs in 5% of patients with critical influenza pneumonia (rupress.org/jem/article/21…; ). 2/ The risk of critical influenza was highest in patients with auto-Abs neutralizing high concentrations of both IFN-alpha2 and IFN-omega (OR=11.7, P=1.3x10-5), especially those <70 yr old (OR=139.9, P=3.1x10-10).

1/ Happy to share a perspective of our 30-year-long journey searching for human genetic and immunological determinants of infectious diseases (sciencedirect.com/science/articl…). 2/ The key question in the field of infectious diseases is paradoxically that of their root cause, as only a small proportion of infected people are severely ill – this is “the infection enigma” (annualreviews.org/doi/abs/10.114…).

1/ Today in @ScienceMagazine, @aspaan1 & colleagues show that human #OTULIN #haploinsufficiency impairs non-leukocytic cell-intrinsic immunity to the #staphylococcal alpha-toxin (science.org/doi/10.1126/sc…). 2/ They discovered OTULIN haploinsufficiency via a genome-wide approach in a cohort of patients with unexplained, life-threatening staphylococcal disease – the findings are relevant in vivo.

1/ In @JExpMed, we report a null IFNAR1 allele that is surprisingly common in western Polynesia, with a MAF>1%. 2/ This work was a fantastic collaboration with @QuintanaMurci, @pittjryan, @morestrada, @LaurentAbel4, @ShenYingZhang1, @JouanguyE, @stutangye, @BeziatV, @JeremyChoin,
@BigioBenedetta, @StatGenDan, @RMaguelonne, @jiechen1982, @tutu_ZQ, and others not on Twitter.

1/ Here is a review in @Nature by the CovidHGE.com of the human #genetic and immunological determinants of life-threatening #COVID-19 (nature.com/articles/s4158…). 2/ We review what has been learned over the last two years about a simple question: why do about 3% of (#unvaccinated) infected people end up in an ICU with critical C-19 pneumonia when 97% of people control the virus well?

1/ In #JoCI/#Springer, @xsolanich & team report #autoAbs neutralizing high concentrations of #type1IFN in 10% of patients with critical #COVID19 pneumonia in their hospital (link.springer.com/article/10.100…). 2/ After Amsterdam (link.springer.com/article/10.100…), Lyon (onlinelibrary.wiley.com/doi/10.1002/ct…), New Haven (nature.com/articles/s4158… ), San Francisco (science.org/doi/10.1126/sc…; link.springer.com/article/10.100…), Boston(sciencedirect.com/science/articl…)…

1/ In this 2nd @SciImmunology paper (immunology.sciencemag.org/content/6/62/e…), we show pre-existing auto-Abs neutralizing low physiological concentrations of type I IFNs account for 15% of critical COVID-19 cases, including 20% of critical cases in patients >80 yrs and 20% of deaths across ages. 2/ We tested 100-fold lower concentrations of type I IFN than in our previous report (science.sciencemag.org/content/370/65…). We also found that, in most patients, these auto-Abs neutralize IFN-alphas and/or -omega, while other patients carry auto-Abs that neutralize IFN-beta only.

1/ In this first @SciImmunology paper (immunology.sciencemag.org/content/6/62/e…), we show that at least 1% of men younger than 60 years with life-threatening COVID-19 are sick because of X-linked recessive (XR) TLR7 deficiency. 2/ In an unbiased burden test, we found TLR7 as the most significant hit on the X chromosome; with very rare (MAF<10e-4) nonsynonymous variants found in patients with critical COVID-19, but not in patients with asymptomatic/mild infection.

We report @JExpMed an international survey of SARS-CoV-2-infected APS-1 patients and show that they are at very high risk of life-threatening, critical C-19 pneumonia due to preexisting auto-Abs neutralizing type I IFNs (urldefense.proofpoint.com/v2/url?u=https…) APS-1 patients typically carry bi-allelic mutations in 𝘈𝘐𝘙𝘌, which controls thymic expression of peripheral antigens, thereby governing central T cell tolerance (science.sciencemag.org/content/298/55…).

We show that neutralizing autoantibodies to type I IFNs underlie a third of the life-threatening adverse reactions to yellow fever virus live-attenuated virus (YFV 17D): rupress.org/jem/article/21… We also report a patient with YFV 17D disease due to inherited IFNAR2 deficiency, consistent with our previous description of a patient with inherited IFNAR1 deficiency: rupress.org/jem/article/21…

We have been silent for a while because our lab and the CHGE were entirely focused on finishing 'twin papers' in @ScienceMagazine about inborn errors of type I IFN or auto-antibodies to type I IFN in nearly 15% of patients with life-threatening #COVID19 😀 science.sciencemag.org/content/369/65… Here is the first paper, which shows that variants in only 13 influenza susceptibility candidate genes that govern TLR3- and IRF7-dependent production of type I IFNs account for at least 3.5% of critical cases of #COVID19 science.sciencemag.org/content/early/… @ScienceMagazine