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Posts by Alessandro Borghesi

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Immune system adaptation during gender-affirming testosterone treatment - Nature Examination of immunological changes in transgender individuals undergoing gender-affirming testosterone treatment reveals sex hormone-regulated pathways in humans and explains sex-divergent responses...

Recent paper (Nature)-why are males more vulnerable to severe infections (ex acute #COVID), while females suffer more from autoimmunity (SLE, MS etc and also #LongCovid)? X/Y or hormones? We study adaptation of immune systems in gender-affirming testosterone treatment: nature.com/articles/s41...

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Cerebral amebiasis due to #Acanthomoeba sp. in a patient with complete gp91phox deficiency. New report from Marie Roelens, Jacinta Bustamante and colleagues @hopitalnecker.bsky.social @institutimagine.bsky.social: rupress.org/jhi/article/...

@esidsociety.bsky.social

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@jenniferuhrlaub.bsky.social, Tiziana Lazzarotto, Patrizia Comoli, Marco Zecca, Stefania Croce, Maria Antonietta Avanzini

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@jfellay.bsky.social

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Alessandro Mancon, Camilla lucca, stefania vogiatzis, Monia Pacenti, Melodie Aubart, Antonio Piralla, Alberto Dolci, Danilo Cereda, Alessandro Aiuti, Emmanuelle Jouanguy, Paul Bastard, and to all the involved Institutions

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Thanks to all co-authors mentioned above and Jacques Fellay,
The Rice Laboratory @ RU, @anne-puel.bsky.social, Laurent Abel, Astrid Marchal, David M Florian, Karin Stiasny, Elisa Burdino, Micol Angelini, Lucy BIZIEN, Daniele Lilleri, Veronica Codullo, Tal Freund, Yael Paran, Avi Gadoth, Roni Biran

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A huge thank you to the Editorial and Production and teams @jhumimmunity.org

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1. IRCCS OSM – InFlaMe

Thanks to our funders and supporters, in particular Fondazione IRCCS Policlinico San Matteo, the Italian Ministry of Health, the Inflame Project (Horizon, EU)
inflame-horizon.eu/who-we-are/f..., @hug-ge.bsky.social

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Overall, our new study replicates, expands and refines our previous findings. This was possible thanks to colleagues from Vienna @aberlejudith.bsky.social &team, Israel (David Hagin &team), Milan (Davide Mileto &team), Pavia (Fausto Baldanti, Irene Cassaniti &team) and others

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At least three independent studies (case report or case series) have reported so far very similar findings
pubmed.ncbi.nlm.nih.gov/38976510/
pubmed.ncbi.nlm.nih.gov/40799617/
pubmed.ncbi.nlm.nih.gov/41354208/

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This was possible by obtaining longitudinal data for several WNVF patients, thanks to Mattia Moratti and Francesca Conti in particular (Bologna).

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Life-Threatening COVID-19: Defective Interferons Unleash Excessive Inflammation The risk of life-threatening COVID-19 pneumonia increases sharply after 65 years of age, but other epidemiological risk factors, genetic or otherwise, are modest. Various rare monogenic inborn errors ...

We also speculate that some patients may initially present with a flu‑like illness (WNVF) and later progress to life‑threatening neuroinvasive disease (WNND) - a two‑step model closely resembling that observed in COVID‑19 pneumonia
www.cell.com/med/fulltext...

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...some patients under this definition of WNVF do, at times, die from WNV infection. We concluded that the high proportion of WNVF cases carrying auto‑Abs reflected, at least in some cases, mis‑assignment to the appropriate WNV disease group.

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With time, studies - and colleagues in hospitals and diagnostic centers - began to include in this WNVF “limbo” all patients with clinical signs who, for various reasons, did not undergo lumbar puncture or imaging to confirm/rule out neurological involvement...
www.acpjournals.org/doi/10.7326/...

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Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey During the 1999 West Nile virus outbreak, thousands of symptomless and symptomatic West Nile viral infections probably occurred, with fewer than 1% resulting in severe neurological disease.

The initial definition of WNVF in the earliest seroepidemiological studies conducted in the USA in the early 2000s referred to individuals tested for WNV serology self-reporting headache or a transient rise in body temperature in the preceding days
www.thelancet.com/journals/lan...

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Simply because these individuals didn’t have mild disease. 👇

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In the 2023 paper, we observed that about 14% of cases (ranging from 0 in some centers to... 30%!! in others) with mild‑to‑moderate WNVF carried these auto‑Abs. Why did these individuals develop a milder form of the disease, despite the presence of the auto‑Abs? 👇

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When, after the 2023 paper, we studied two new Italian cohorts from the 2023 summer outbreak, we were “happy” to see that we could replicate the ~40% auto‑Ab finding. This was already important. But we could not explain yet one finding on mild‑to‑moderate cases with WNV fever (WNVF).

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The 2023 paper was already convincing. Then why replicate and expand it? We could have not, but we did. If you’ve been on top of Everest, don’t you also want to be on top of K2 at some point? Useless to explain that replication and refinement are not optional in Science.

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...Hungary (@Anna Nagy, @yannick-simonin.bsky.social ), and Texas (@KristyOMurray).

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These studies could not have been possible without the co‑leadership of the @casanovalab.bsky.social, and the crucial contributions of colleagues from Italy (Padova @luisabarzon.bsky.social [the largest cohort studied so far for these auto‑Abs] Bologna @GiadaRossini and Torino @ValeriaGhisetti)...

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Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients Gervais et al. show that auto-Abs neutralizing type I IFNs and pre-existing infection underlie ∼40% of cases of West Nile virus (WNV) encephalitis. Blood a

Results were published in 2023 @jem.org, showing that ~40% (15–50) of WNV encephalitis (one out of two patients who died of WNV) carried these auto‑Abs. We performed experiments that provided indirect but compelling evidence for a causative role of these auto‑Abs.
rupress.org/jem/article/...

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COVID HUMAN GENETIC EFFORT COVID Human Genetic Effort is an international consortium aiming to discover inborn errors of immunity underlying severe forms of COVID-19 in previously healthy individuals

Despite very different, many epidemiological features of WNV encephalitis, incl. WNV‑related mortality by age (J‑shaped) and sex, make it strikingly similar to COVID-19 pneumonia, which studies from the www.covidhge.com had shown to be caused by auto Abs neutralizing type I IFNs in ~15% of cases.

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In 2022, during an intense WNV summer outbreak, we discovered that a surprisingly high proportion of patients with WNV encephalitis (about half of our initial cohort) carry auto‑Abs neutralizing type I IFNs. Why did we choose to study WNV infection for auto‑Abs to type I IFNs? 👇

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Auto-Abs neutralizing type I INFs in ~40% of patients with West Nile virus (WNV) encephalitis – the sequel @jhumimmunity.org with A Gervais, F Trespidi, A Ferrari, F Rovida, A Cobat, @shenyingzhang1.bsky.social , @casanovalab.bsky.social and co-authors mentioned👇in thread
rupress.org/jhi/article/...

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Our new study @jhumimmunity.org - detailed thread will follow !

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Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts In 13 cohorts of individuals with WNV infection, the risk of WNV encephalitis is increased 20 to >>2,000 times by circulating auto-Abs neutralizing t

1/ Which human infectious disease is best understood in 2026? West Nile virus encephalitis, with 40% of cases attributed causally and mechanistically to auto-Abs neutralizing type I IFNs. doi.org/10.70962/jhi...

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Congratulations !!! 👏

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Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts In 13 cohorts of individuals with WNV infection, the risk of WNV encephalitis is increased 20 to >>2,000 times by circulating auto-Abs neutralizing t

Autoantibodies neutralizing type I IFNs in 40% of patients with WNV encephalitis in seven new cohorts url: rupress.org/jhi/article/...

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Rare variants in CYBB (encoding gp91phox) are responsible for chronic granulomatous disease. In @jhumimmunity.org, Roelens, Bustamante et al. report a patient affected by multiple cerebral abscesses caused by #Acanthamoeba sp. and complete gp91phox deficiency. rupress.org/jhi/article/...

#CGD

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