Browsing by Subject "Immunity"

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    Exosomes: Natural nanovesicle candidates used in the diagnosis and treatment
    (Turkish Society of Immunology, 2013) Kahraman, T.; Gíiçlíiler G.; Gürsel I.
    Exosomes are nano-vesicles released by all known cells. Although they were called as residual cells acting as a cleaner of undesired molecules out of cell during the first discovery in 1980s, recent studies have revealed critical physiological tasks of these vesicles over the past 20 years. These vesicles which can be produced by all body fluids play an important role in many biological activities including intracellular communication, signal conduction, genetic material transfer, and regulation of immune response. Due to their several tasks, exosomes play a crucial role in the disease pathogenesis. Considering all these tasks, exosomes can be considered in both diagnosis and treatment. Exosomes originating from distinct cells have immunosuppressive and immunostimulatory features and, thereby, therapeutic attempts which regulate immune function in case of autoimmune and immunosuppression. In addition, thanks to being natural nano-carriers, exosomes may pave the way for the development of new-generation vaccines containing both adjuvant and antigen. Besides therapeutic applications, there are evidences indicating that exosomes can be used in the diagnosis of several cancer forms including prostate cancer, glioblastoma, squamous-cell lung carcinoma and hepatocellular carcinoma, as they play a role in the disease pathogenesis. © 2014 Turkish Journal of Immunology.
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    Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
    (BioMed Central Ltd., 2023-04-05) Matuozzo D.; Talouarn E.; Marchal A.; Zhang P.; Manry J.; Seeleuthner Y.; Zhang Y.; Bolze A.; Chaldebas M.; Milisavljevic B.; Gervais A.; Bastard P.; Asano T.; Bizien L.; Barzaghi F.; Abolhassani H.; Tayoun A.A.; Aiuti A.; Darazam I.A.; Allende L.M.; Alonso-Arias R.; Arias A.A.; Aytekin G.; Bergman P.; Bondesan S.; Bryceson Y.T.; Bustos I.G.; Cabrera-Marante O.; Carcel S.; Carrera P.; Casari G.; Chaïbi K.; Colobran R.; Condino-Neto A.; Covill L.E.; Delmonte O.M.; Zein L.E.; Flores C.; Gregersen P.K.; Gut M.; Haerynck F.; Halwani R.; Hancerli S.; Hammarström L.; Hatipoğlu N.; Karbuz A.; Keles S.; Kyheng C.; Leon-Lopez R.; Franco J.L.; Mansouri D.; Martinez-Picado J.; Akcan O.M.; Migeotte I.; Morange P.-E.; Morelle G.; Martin-Nalda A.; Novelli G.; Novelli A.; Özçelik Tayfun; Palabiyik F.; Pan-Hammarström Q.; de Diego R.P.; Planas-Serra L.; Pleguezuelo D.E.; Prando C.; Pujol A.; Reyes L.F.; Rivière J.G.; Rodriguez-Gallego C.; Rojas J.; Rovere-Querini P.; Schlüter A.; Shahrooei M.; Sobh A.; Soler-Palacin P.; Tandjaoui-Lambiotte Y.; Tipu I.; Tresoldi C.; Troya J.; van de Beek D.; Zatz M.; Zawadzki P.; Al-Muhsen S.Z.; Alosaimi M.F.; Alsohime F.M.; Baris-Feldman H.; Butte M.J.; Constantinescu S.N.; Cooper M.A.; Dalgard C.L.; Fellay J.; Heath J.R.; Lau Y.-L.; Lifton R.P.; Maniatis T.; Mogensen T.H.; von Bernuth H.; Lermine A.; Vidaud M.; Boland A.; Deleuze J.-F.; Nussbaum R.; Kahn-Kirby A.; Mentre F.; Tubiana S.; Gorochov G.; Tubach F.; Hausfater P.; Meyts I.; Zhang S.-Y.; Puel A.; Notarangelo L.D.; Boisson-Dupuis S.; Su H.C.; Boisson B.; Jouanguy E.; Casanova J.-L.; Zhang Q.; Abel L.; Cobat A.
    Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7 dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identifed in~80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide signifcance. Under a recessive model, the most signifcant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P=1.1× 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 infuenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3–8.2], P=2.1× 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1–2635.4], P=3.4× 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3–8.4], P=7.7× 10−8). Finally, the patients with pLOF/ bLOF variants at these 15 loci were signifcantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68× 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.