#auto-anticorps

  • Off-target immune response could predict #COVID-19 severity
    https://medicalxpress.com/news/2021-09-off-target-immune-response-covid-severity.html

    Led by researchers at NYU Grossman School of Medicine, the study detected the autoimmune antibodies in the blood of more than a third of men and women on admission to hospital and confirmed to have the disease.

    Among the new study findings is that a subset of these autoimmune antibodies that bind to DNA or to a particular type of fat molecule, a lipid called #phosphatidylserine, [known to spill into the bloodstream as cells are killed by disease, such as COVID-19] were more often twice as abundant at the start of coronavirus infection in those whose conditions worsened quickly than in those whose health did not decline. Patients with these elevated levels of autoimmune antibodies were five to seven times more likely to develop severe disease than those whose antibodies levels were stable.

    […]

    If found to be causal of cell damage, new COVID-19 treatments could include antibody injections from healthy donors to dilute the presence of autoimmune antibodies. Other experimental therapies under consideration involve biodegradable antigens that attach to autoimmune antibodies and neutralize them, but do not lead to a lasting antibody immune reaction of their own.

    Source
    Claudia Gomes et al, Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19, Life Science Alliance (2021).
    https://www.life-science-alliance.org/content/4/11/e202101180

    #auto-anticorps

  • COVID-19 : jusqu’à 20% des formes graves liées à des #auto-anticorps ?
    http://francais.medscape.com/voirarticle/3607518

    Cette découverte est d’autant plus intéressante qu’en étudiant la distribution de ces auto-anticorps dans la population générale non infectée, les chercheurs se sont aperçus que leur présence est très rare avant 65 ans (0,2 à 0,5%) et augmente ensuite exponentiellement avec l’âge. Pour cela, ils ont comparé plus de 34 000 individus sains, classés par sexe et tranche d’âge, issus de cohortes de l’Inserm, de l’Etablissement français du sang, et de Cerba Healthcare, partenaire du laboratoire de génétique humaine des maladies infectieuses. Il en ressort que la distribution des auto-anticorps atteint 4% entre 70 et 79 ans, et 7% entre 80 et 85 ans. Ces résultats pourraient expliquer, au moins en partie, pourquoi l’âge est un facteur de risque majeur dans le développement de formes graves de Covid-19.

    […]

    Parallèlement, d’autres recherches vont également dans le sens d’une implication d’un déficit en IFN-1 dans les formes graves de Covid-19. Elles ont montré que chez les hommes, 1,3% de ces formes sévères s’expliquent par des anomalies génétiques du gène TLR7 qui joue un rôle majeur dans le mécanisme de production d’IFN-1.

    Sources :

    Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths | Science Immunology
    https://immunology.sciencemag.org/content/6/62/eabl4340.full

    X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19 | Science Immunology
    https://immunology.sciencemag.org/content/6/62/eabl4348.full

  • Scientists begin to unravel the mysteries of the coronavirus and brains - The Washington Post
    https://www.washingtonpost.com/health/2021/06/07/covid-are-brains-affected

    In laboratory experiments, the coronavirus can infiltrate neurons and other brain cells when those cells are cultured. It also can invade clumps of cells designed to replicate the structure of a brain, which scientists call organoids. Those observations suggest brains are vulnerable to invasion by SARS-CoV-2.

    At least in theory. Not all brain specialists are convinced that what can happen in a petri dish occurs in sick humans.

    “Frankly, I don’t think it tells us a lot about what’s going on in the brains of people who were infected with this virus,” said James E. Goldman, a neuropathologist and a colleague of Thakur and Canoll at Columbia. [COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital | Brain | Oxford Academic
    https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab148/6226391]

    As that trio and their co-authors reported in the journal Brain in April, they did not find viral proteins in brain autopsies.

    They detected no or low levels of viral RNA, depending on the technique used. Canoll suggested the viral genetic material they did find in the brain came from virus in the membrane that surrounds the brain, not from within the organ itself.

    “This, alongside other studies, is suggestive that there’s not a florid amount of virus in the brain in patients who have died,” said Thakur, lead author of that study.

    [...]

    Although there wasn’t much virus to be found, the brains of people killed by the coronavirus weren’t unscathed . The Columbia researchers, looking at thin slices of brain tissue under microscopes, found two main types of problems in patients who died of covid.

    First were infarctions, dead tissue surrounding blocked blood vessels, found in the brain’s gray matter. [...]

    The second issue, appearing in the brainstem, cerebellum and other areas, involved swarms of immune cells. Those cells often converged around dead or dying neurons. “They’re actually attacking and eating the neurons,” Canoll said.

    These immune cells, called microglia, were enlarged and had clustered in nodules, signaling inflammation, though not as severe as what pathologists see in cases of viral encephalitis. Curiously, there was no virus in the neurons being surrounded.

    Still, microglia don’t act like this unless provoked.

    “Something is triggering them to do that,” said immunologist Lena Al-Harthi, who studies at Rush University in Chicago how HIV affects the central nervous system. That trigger remains unknown, but Harthi suggested it could be an autoimmune response .

    ]...] Autoantibodies have been found in postmortem brains and the cerebrospinal fluid of covid patients , Harthi said.

    It’s unclear whether the pathologies seen in these autopsies could also occur in patients with mild cases, or long-term symptoms. Goldman declined to speculate. These patients, many of whom were admitted to intensive care, had died of severe covid-19.

    “This is a series of a small subset of patients, so there’s a selection issue,” Thakur said. But with that caveat and others — variants are spreading that weren’t in the initial wave of the pandemic, for example — she said the results are suggestive that the virus “isn’t entering and propagating and infecting the brain.

    The scientists are working on a follow-up study examining the brains of patients who had covid and recovered but later died. Those observations should help settle whether brains in very sick patients resemble brains in other cases.

    [..,]

    Compared with almost all other diseases, covid-19 has been studied with unprecedented focus. [...]

    The scientists used tools not typically applied across the brain.

    We’ve already started to look at the brains of patients that don’t have covid” but died of other severe lung diseases, Canoll said. They are seeing pathological changes reminiscent of what they detected in brains from people who died of covid.

    [...]

    Joanna Hellmuth, a cognitive neurologist at the UCSF Memory and Aging Center, said she hears the same story repeatedly from previously healthy young adults who tell her that after even a mild case of covid: “My brain doesn’t work like it used to.”

    Hellmuth said cognitive impairment is showing up in people who measure well in mood testing, suggesting their symptoms are not caused by depression or another psychiatric problem. She has seen similar patterns caused by other viruses

    #neurologie #covid-19 #auto-anticorps

  • Diverse Functional Autoantibodies in Patients with COVID-19 | Nature
    https://www.nature.com/articles/s41586-021-03631-y

    We found that #COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of #SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.

    #auto-anticorps

  • Coronavirus Deranges the Immune System in Complex and Deadly Ways | Kaiser Health News
    https://khn.org/news/article/covid-autoimmune-virus-rogue-antibodies-cytokine-storm-severe-disease

    In some people with severe covid, however, helper T cells don’t stand down when the infection is over, said James Heath, a professor and president of Seattle’s Institute for Systems Biology.

    About 10% to 15% of hospitalized covid patients Heath studied had high levels of these cells even after clearing the infection. By comparison, Heath found lingering helper T cells in fewer than 5% of covid patients with less serious infections.

    In affected patients, helper T cells were still looking for the enemy long after it had been eliminated. Heath is now studying whether these overzealous T cells might inflict damage that leads to chronic illness or symptoms of autoimmune disease.

    “These T cells are still there months later and they’re aggressive,” Heath said. “They’re on the hunt.”

    [...]

    New research shows that the coronavirus may activate preexisting autoantibodies, as well as prompt the body to make new ones.

    In the January study**, half of the hospitalized covid patients had autoantibodies, compared with fewer than 15% of healthy people. While some of the autoantibodies were present before patients were infected with SARS-CoV-2, others developed over the course of the illness.

    **https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852238

    [...]

    Dr. Shiv Pillai, a Harvard Medical School professor, notes that autoantibodies aren’t uncommon. Many healthy people walk around with dormant autoantibodies that never cause harm.

    For reasons scientists don’t completely understand, viral infections appear able to tip the scales, triggering autoantibodies to attack, said Dr. Judith James, vice president of clinical affairs at the Oklahoma Medical Research Foundation and a co-author of Luning Prak’s study.

    #auto-anticorps #auto-immunité #covid-19

    • sur les aspects induction de réaction auto-immune, les traitements « préventifs » ou immuno-depressifs existants serait-ils ainsi justifiés post-fact ?

  • Les formes sévères de #Covid-19 seraient liées à une réponse #anticorps de type auto-immune
    https://theconversation.com/les-formes-severes-de-covid-19-seraient-liees-a-une-reponse-anticor

    Durant les premiers temps de la pandémie, de nombreux immunologistes, dont moi-même, ont supposé que les patients qui produisaient de grandes quantités d’anticorps suffisamment tôt au cours de l’infection par le coronavirus SARS-CoV-2 ne développeraient pas la maladie. Nous nous sommes trompés. Après plusieurs mois passés à étudier la Covid-19, comme d’autres scientifiques, j’ai fini par réaliser que la situation est en réalité bien plus compliquée que ce que je pensais initialement.

    #immunité #auto-anticorps

  • Découverte d’anomalies immunologiques et génétiques associées à des formes sévères de #Covid-19 – Réalités Biomédicales
    https://www.lemonde.fr/blog/realitesbiomedicales/2020/09/27/decouverte-danomalies-immunologiques-et-genetiques-associees-a-des-formes-se

    La présence d’#auto-anticorps (IgG) dirigés contre au moins un #interféron de type I a été détectée chez 13,7 % des patients (135 sur 987) présentant une forme #critique de Covid-19. [...] Des auto-anticorps dirigés contre les interférons de type I ont également été détectés dans des échantillons de plasma sanguin prélevés chez des patients avant qu’ils aient développé la Covid-19, ce qui montre que la production des auto-anticorps n’a pas été déclenchée par l’infection par le #SARS-CoV-2.

    Les chercheurs [...] rapportent que 101 des 987 patients présentant une forme #sévère de Covid-19, soit chez 10,2 % d’entre eux, possèdent des auto-anticorps (IgG) capables de neutraliser au moins un interféron de type I.

    [...] En revanche, ces auto-anticorps n’ont été trouvés que chez 4 des 1227 sujets sains (0,3 %) et chez aucun des 663 patients présentant une infection asymptomatique ou modérée par le SARS-CoV-2.

    [...]

    Implications cliniques

    Tout d’abord, estiment les chercheurs, la détection des auto-anticorps dirigés contre les interférons de type I pourrait permettre d’identifier les patients infectés par le SARS-CoV-2 présentant un risque de développer une forme critique de la maladie Covid-19.

    Ensuite, en cas de guérison, le plasma de ces patients (pouvant contenir des auto-anticorps) ne devrait pas être utilisé dans le cadre des essais cliniques en cours visant à administrer le plasma de patients convalescents pour traiter des personnes atteintes de Covid-19 .

    Par ailleurs, ajoutent les auteurs, on peut imaginer d’utiliser des techniques permettant d’éliminer sélectivement les auto-anticorps ou les cellules qui les produisent***.

    Enfin, un traitement par interféron-bêta, par voie injectable ou inhalée, pourrait être bénéfique dans la mesure où il est rare que des patients porteurs d’auto-anticorps contre les IFN-I développent des auto-anticorps vis-à-vis de cette autre catégorie d’interférons, concluent-ils.

    [...]

    Défauts génétiques

    L’équipe franco-américaine, qui appartient au consortium international du COVID Human Genetic Effort, a publié dans Science un second article. Cette fois, les chercheurs ont recherché la présence d’anomalies sur des gènes responsables de la synthèse des interférons de type I chez des patients présentant une forme critique de Covid-19, faisant l’hypothèse [ en fait déjà vérifiée par d’autres auteurs ] que la sévérité de la maladie pouvait, chez certains patients, être imputable à ces variants génétiques. [...]

    Les chercheurs rapportent que 3,5 % des patients qui présentaient une forme critique de Covid-19 étaient porteurs d’une anomalie génétique affectant la réponse immunitaire dépendante des interférons de type I. De façon surprenante, ces défauts génétiques (dont certains peuvent être délétères en cas d’infection grippale) sont restés silencieux et n’ont pas eu d’impact clinique jusqu’au moment de l’infection par le SARS-CoV-2 [...]

    #immunité

    Auto-antibodies against type I IFNs in patients with life-threatening COVID-19 | Science
    https://science.sciencemag.org/content/early/2020/09/23/science.abd4585.full

    Inborn errors of type I IFN immunity in patients with life-threatening COVID-19 | Science
    https://science.sciencemag.org/content/early/2020/09/25/science.abd4570.full

    • One in Seven Dire COVID Cases May Result from a Faulty Immune Response - Scientific American
      https://www.scientificamerican.com/article/one-in-seven-dire-covid-cases-may-result-from-a-faulty-immune-re

      Perhaps the most immediate implication of the new studies concerns the use of convalescent plasma, an experimental treatment made from the blood of people who have recovered from COVID-19. In August the U.S. Food and Drug Administration issued a controversial “emergency use authorization” for the blood product. Zúñiga points out that it would be important to screen plasma donors for auto-antibodies. “If you have severe COVID-19, would you like to receive antibodies that neutralize an antiviral response?” she asks. “No thank you.”

      Given the growing evidence that interferon plays a crucial role in arresting severe infection, Fish believes that treating COVID-19 patients with interferon, regardless of their antibody or genetic status, could be a winning tactic, particularly early in the infection. She points to exploratory studies on interferon in Cuba and Wuhan, China, that showed promising effects on mortality rates and earlier clearance of the virus.

      But determining the #timing and other details of such treatment will be vital. “Interferon can be a double-edged sword in many infections,” Zúñiga says. “It activates many immune cells, but it can enhance inflammation as well. And it can have a negative immunoregulatory role, activating factors that suppress the immune response.”

      Experts seem to agree that interferons would have to be given early to help shut down the infection. Once a patient develops an extreme immune reaction sometimes called a “cytokine storm,” interferons are unlikely to be of use, Fish says.

      Dozens of COVID-19 clinical trials are already underway to test the efficacy of various types of interferon therapies, which can be given as a nasal spray or injection. One large study, conducted by the National Institute of Allergy and Infectious Diseases, is comparing the antiviral remdesivir alone with a combined therapy of the drug and interferon-beta. And Fish is involved in a study in Santiago, Chile, that will investigate whether giving interferons to members of a household where someone has been infected with the coronavirus could prevent them from falling ill. It remains to be seen whether any of these therapies pan out, but the new findings at least unlock one more piece of the COVID-19 puzzle.