Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(2)

Published: Jan. 4, 2024

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only three, plus IFN-ω five, and IFN-α2, IFN-β two; nine patients). Seven (3.8%) Abs at least ng/ml one IFN, whereas the other 12 (6.6%) 100 pg/ml. The auto-Abs neutralized both unglycosylated glycosylated IFNs. also detected pg/ml 4 2,267 uninfected (0.2%) 45 (2%). odds ratios (ORs) life-threatening were, therefore, higher (OR [95% CI] = 67.6 [5.7-9,196.6]) than 2.6 [1.2-5.3]). ORs were high concentrations 12.9 [4.6-35.9]) those low 5.5 [3.1-9.6]) and/or IFN-α2.

Language: Английский

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The ouroboros of autoimmunity

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(5), P. 743 - 754

Published: May 1, 2024

Language: Английский

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Human immunity

Published: Feb. 26, 2025

Due to the burden of infectious diseases, human life expectancy at birth remained about 20–25 years until end 19th century, implying that host defense—which operates individual level, and only poorly that—is barely sufficient population level. Microbes preceded us by three billion evolve much more rapidly. Moreover, protective immunity has been selected evolutionary cost allergy, autoinflammation, autoimmunity. It is therefore no exaggeration predict almost all humans carry inborn errors immunity, with insufficient or excessive responses some environmental triggers, otherwise. Thanks remarkable power its concepts recent progress in methods, genetics finally made it possible investigate mechanisms molecular cellular levels. Human provide countless opportunities analyze derailments natural conditions, an unprecedented scale, are thus a unique asset from both biological medical perspectives. Hence, Journal Immunity.

Language: Английский

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The Microbe, the Infection Enigma, and the Host

Annual Review of Microbiology, Journal Year: 2024, Volume and Issue: 78(1), P. 103 - 124

Published: July 10, 2024

Human infectious diseases are unique in that the discovery of their environmental trigger, microbe, was sufficient to drive development extraordinarily effective principles and tools for prevention or cure. This medical prowess has outpaced, perhaps even hindered, scientific progress equal magnitude biological understanding diseases. Indeed, hope kindled by germ theory disease rapidly subdued infection enigma, need a host solution, when it realized most individuals infected with agents continue do well. The root causes death unhappy few remained unclear. While canonical approaches vitro (cellular microbiology), vivo (animal models), natura (clinical studies) analyzed consequences considered be cause disease, cells, tissues, organisms seen as uniform host, alternative searched preexisting particularly human genetic immunological determinants populations diverse trigger microbe.

Language: Английский

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Aire in Autoimmunity

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 427 - 53

Published: Feb. 16, 2024

The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly era advanced single-cell genomics. We briefly describe human genetics discovery Aire, as well function gained from genotype-phenotype correlations spectrum Aire-associated autoimmunity-including patients with Aire mutations broad diverse implications for health. then highlight emerging trends biology, focusing on three topic areas. First, we discuss medullary epithelial diversity development. Second, recent developments regarding molecular mechanisms binding partners. Finally, rapidly evolving identity extrathymic Aire-expressing cells (eTACs), a novel eTAC subset called Janus cells, their potential roles homeostasis.

Language: Английский

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Interferon at the crossroads of SARS-CoV-2 infection and COVID-19 disease

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(8), P. 104960 - 104960

Published: June 24, 2023

A novel coronavirus now known as SARS-CoV-2 emerged in late 2019, possibly following a zoonotic crossover from present bats. This virus was identified the pathogen responsible for severe respiratory disease, disease-19 (COVID-19), which of May 2023, has killed an estimated 6.9 million people globally according to World Health Organization. The interferon (IFN) response, cornerstone antiviral innate immunity, plays key role determining outcome infection by SARS-CoV-2. review considers evidence that leads IFN production; replication is sensitive action; molecular mechanisms antagonizes and how genetic variability human host affects response at level production or action both. Taken together, current understanding suggests deficiency effective important determinant underlying some cases critical COVID-19 disease IFNλ IFNα/β have potential therapeutics treatment infection.

Language: Английский

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Human determinants of age-dependent patterns of death from infection

Immunity, Journal Year: 2024, Volume and Issue: 57(7), P. 1457 - 1465

Published: July 1, 2024

Regardless of microbial virulence (i.e., the global infection-fatality ratio), age generally drives prevalence death from infection in unvaccinated humans. Four mortality patterns are recognized: common U- and L-shaped curves endemic infections unique W- J-shaped pandemic infections. We suggest that these result different sets human genetic immunological determinants. In this model, it is interplay between (1) monogenic genotypes affecting immunity to primary preferentially manifest early life related or their phenocopies, including auto-antibodies, which later (2) occurrence persistence adaptive, acquired cross-reactive infections, shapes age-dependent pattern deaths infection.

Language: Английский

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Type I interferon pathway genetic variants in severe COVID-19

Virus Research, Journal Year: 2024, Volume and Issue: 342, P. 199339 - 199339

Published: Feb. 22, 2024

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2. According to the World Health Organization (WHO), there have been over 760 million reported cases and 6 deaths this worldwide. The severity of COVID-19 based on symptoms presented patient divided as asymptomatic, mild, moderate, severe, critical. manifestations are interconnected with genetic variations. innate immunity quickest response mechanism organism against viruses. Type I interferon pathway plays a key role in antiviral responses due viral replication inhibition infected cells adaptive stimulation induced molecules. Thus, variants type pathway's genes being studied different manifestations. This review summarizes prognosis progression COVID-19.

Language: Английский

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From second thoughts on the germ theory to a full-blown host theory

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(26)

Published: June 12, 2023

In 1955, René Dubos famously expressed his “second thoughts on the germ theory”, attributing infectious diseases to various “changing circumstances” that weaken host by unknown mechanisms. He rightly stressed only a small minority of individuals infected almost any microbe develop clinical disease. Intriguingly, though, he did not mention abundant and elegant findings reported from 1905 onward unambiguously pointed genetic determinants infection outcome in plants animals, including human inborn errors immunity. Diverse over next 50 y corroborated extended these earlier immunological observations had neglected. Meanwhile, sequential advent immunosuppression- HIV–driven immunodeficiencies unexpectedly provided mechanistic basis for own views. Collectively, two lines evidence support theory diseases, with inherited acquired as key severe outcome, relegating an environmental trigger reveals underlying preexisting cause disease death.

Language: Английский

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The role of interferon in the thymus

Current Opinion in Immunology, Journal Year: 2023, Volume and Issue: 84, P. 102389 - 102389

Published: Sept. 20, 2023

Language: Английский

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