Paraneoplastiline autoimmuunsus

Paraneoplastilist autoimmuunsust on täheldatud peaaegu kõikide kasvajate korral, kuid selle väljendused ning patogenees on väga varieeruvad. Autoimmuunne kahjustus võib tabada eri elundisüsteeme: tuntakse neuroloogilisi, dermatoloogilisi, hematoloogilisi, reumatoloogilisi ja süsteemseid sündroome. Tekkemehhanismidest eristatakse neoplastilisi tsentraalse immuuntolerantsuse häireid, perifeerse immuuntolerantsuse iseärasusi ning antigeenide avaldumishäireid. Paraneoplastilised sündroomid võivad nii eelneda kui ka järgneda kasvaja diagnoosile või koguni viidata veel avastamata kasvaja paikmele. Autoimmuunsed nähud võivad kaduda või taandareneda põhihaiguse ravi järel, kuid mõnedel juhtudel peab kiiresti alustama immuunsupresseerivat ravi, et vältida pöördumatute kahjustuste teket. Paraneoplastilise autoimmuunsusega patsientidel on kirjeldatud paremat prognoosi võrreldes nendega, kellel sama kasvaja esineb isoleeritult. Arvatavasti peegeldab autoimmuunsus sel puhul tugevamat immuunvastust ka kasvaja enese vastu.Eesti Arst 2017; 96(5):259–26

Hüper-IgE-sündroom – primaarse immuunpuudulikkuse haruldane vorm

Hüperimmunoglobuliin-E-sündroom (HIES) on primaarse immuunpuudulikkuse haruldane vorm, millele on iseloomulik klassikaline sümptomitriaad: nahalööve, korduv raske pneumoonia ning seerumi üld-IgE-sisalduse suurenemine. Nelja-aastasel tüdrukul, kes põdes raskeid hingamisteede infektsioone, kandidoosi ja kelle vereseerumi üld-IgE-sisaldus oli suurenenud, diagnoositi HIES, kuigi tal tüüpilist löövet ei olnud. Tegemist on Eestis esimest korda geneetiliselt kinnitatud hüperimmunoglobuliin- E-sündroomiga.Eesti Arst 2014; 93(9):521–52

Response to comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'

In 2016, we reported four substantial observations of APECED/APS1 patients, who are deficient in AIRE, a major regulator of central T cell tolerance (Meyer et al., 2016). Two of those observations have been challenged. Specifically, 'private' autoantibody reactivities shared by only a few patients but collectively targeting >1000 autoantigens have been attributed to false positives (Landegren, 2019). While acknowledging this risk, our study-design included follow-up validation, permitting us to adopt statistical approaches to also limit false negatives. Importantly, many such private specificities have now been validated by multiple, independent means including the autoantibodies ' molecular cloning and expression. Second, a significant correlation of antibody-mediated IFN a neutralization with an absence of disease in patients highly disposed to Type I diabetes has been challenged because of a claimed failure to replicate our findings (Landegren, 2019). However, flaws in design and implementation invalidate this challenge. Thus, our results present robust, insightful, independently validated depictions of APECED/APS1, that have spawned productive follow-up studies.Non peer reviewe

Antiviral efficacy of nanomaterial-treated textiles in real-life like exposure conditions

We thank the following people and institutions for their contribution to our investigation. Toomas Varjund from TAD Logistics OÜ for providing the textiles. Ülis Sõukand from Estonian Environmental Research Center for his help with methods of chemical analysis. Estonian Research Council projects COVSG2, PRG629, PRG1496, PRG1154 and European Commission project STOP (Grant agreement ID: 101057961) for their financial support. The Center of nanomaterials technologies and research (NAMUR+) for core facility funded by project TT13 which was used conducting the research.Due to the growing interest towards reducing the number of potentially infectious agents on critical high-touch surfaces, the popularity of antimicrobially and antivirally active surfaces, including textiles, has increased. The goal of this study was to create antiviral textiles by spray-depositing three different nanomaterials, two types of CeO2 nanoparticles and quaternary ammonium surfactant CTAB loaded SiO2 nanocontainers, onto the surface of a knitted polyester textile and assess their antiviral activity against two coronaviruses, porcine transmissible gastroenteritis virus (TGEV) and severe acute respiratory syndrome virus (SARS CoV-2). Antiviral testing was carried out in small droplets in semi-dry conditions and in the presence of organic soiling, to mimic aerosol deposition of viruses onto the textiles. In such conditions, SARS CoV-2 stayed infectious at least for 24 h and TGEV infected cells even after 72h of semi-dry deposition suggesting that textiles exhibiting sufficient antiviral activity before or at 24 h, can be considered promising. The antiviral efficacy of nanomaterial-deposited textiles was compared with the activity of the same nanomaterials in colloidal form and with positive control textiles loaded with copper nitrate and CTAB. Our results indicated that after deposition onto the textile, CeO2 nanoparticles lost most of their antiviral activity, but antiviral efficacy of CTAB-loaded SiO2 nanocontainers was retained also after deposition. Copper nitrate deposited textile that was used as a positive control, showed relatively high antiviral activity as expected. However, as copper was effectively washed away from the textile already during 1 h, the use of copper for creating antiviral textiles would be impractical. In summary, our results indicated that antiviral activity of textiles cannot be predicted from antiviral efficacy of the deposited compounds in colloid and attention should be paid on prolonged efficacy of antivirally coated textiles.--//-- Alexandra Nefedova, Kai Rausalu, Eva Zusinaite, Vambola Kisand, Mati Kook, Krisjanis Smits, Alexander Vanetsev, Angela Ivask, Antiviral efficacy of nanomaterial-treated textiles in real-life like exposure conditions, Heliyon, Volume 9, Issue 9, 2023, e20067, ISSN 2405-8440, https://doi.org/10.1016/j.heliyon.2023.e20067. Published under the CC BY-NC-ND licence.Estonian Research Council projects COVSG2, PRG629, PRG1496, PRG1154; European Commission project STOP (Grant agreement ID: 101057961); the Institute of Solid State Physics, University of Latvia has received funding from EU CAMART2 project (European Union's Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017 TeamingPhase2 under grant agreement No. 739508

Downi sündroom – immuunsüsteemi häiretega kromosoomihaigus

Downi sündroomi (DS) ehk 21. kromosoomi trisoomia korral esineb mitmesuguseid haigusnähte, millest osa on seotud immuunsüsteemi funktsiooni häiretega. Artiklis käsitletud uuringust ilmnes, et 15aastastel ja vanematel DS-haigetel esineb tuumavastaseid ning retikuliinivastaseid antikehi oluliselt sagedamini kui tervetel. Üksikutel haigetel leiti ka pankrease saarekeste, kilpnäärme ja mao parietaalrakkude vastaseid autoantikehi. Perifeerse vere rakkude hulgas oli DS-haigetel märkimisväärselt suurenenud mälufunktsiooni omavate CD45RO+ lümfotsüütide hulk, mis võib olla üheks autoimmuunnähtude sagedasema esinemise põhjuseks neil haigetel. Eesti Arst 2007; 86(8):506-51

Delineating the Healthy Human Skin UV Response and Early Induction of Interferon Pathway in Cutaneous Lupus Erythematosus

Non peer reviewe

Antiviral efficacy of cerium oxide nanoparticles

The authors gratefully acknowledge the financial support by the Estonian Research Council Grants (COVSG2, PRG629, PRG1496), Estonian Centre of Excellence in Research project “Advanced materials and high-technology devices for sustainable energetics, sensorics and nanoelectronics” TK141 (2014-2020.4.01.15-0011) and University of Tartu Development Fund (PLTFYARENG53). The research was partly conducted using the NAMUR+ core facility funded by projects “Center of nanomaterials technologies and research” (2014-2020.4.01.16-0123) and TT13.Nanomaterials are prospective candidates for the elimination of viruses due to their multimodal mechanisms of action. Here, we tested the antiviral potential of a largely unexplored nanoparticle of cerium dioxide (CeO2). Two nano-CeO2 with opposing surface charge, (+) and (−), were assessed for their capability to decrease the plaque forming units (PFU) of four enveloped and two non-enveloped viruses during 1-h exposure. Statistically significant antiviral activity towards enveloped coronavirus SARS-CoV-2 and influenza virus was registered already at 20 mg Ce/l. For other two enveloped viruses, transmissible gastroenteritis virus and bacteriophage φ6, antiviral activity was evidenced at 200 mg Ce/l. As expected, the sensitivity of non-enveloped viruses towards nano-CeO2 was significantly lower. EMCV picornavirus showed no decrease in PFU until the highest tested concentration, 2000 mg Ce/l and MS2 bacteriophage showed slight non-monotonic response to high concentrations of nano-CeO2(−). Parallel testing of antiviral activity of Ce3+ ions and SiO2 nanoparticles allows to conclude that nano-CeO2 activity was neither due to released Ce-ions nor nonspecific effects of nanoparticulates. Moreover, we evidenced higher antiviral efficacy of nano-CeO2 compared with Ag nanoparticles. This result along with low antibacterial activity and non-existent cytotoxicity of nano-CeO2 allow us to propose CeO2 nanoparticles for specific antiviral applications. © 2022, The Author(s). --//-- This is an open access article Nefedova A, Rausalu K, Zusinaite E, Vanetsev A, Rosenberg M, Koppel K, Lilla S, Visnapuu M, Smits K, Kisand V, Tätte T, Ivask A., "Antiviral efficacy of cerium oxide nanoparticles", Scientific Reports (2022); 12(1):18746, doi: 10.1038/s41598-022-23465-6 published under the CC BY 4.0 licence.Estonian Research Council Grants (COVSG2, PRG629, PRG1496); Estonian Centre of Excellence in Research TK141 (2014-2020.4.01.15-0011); University of Tartu Development Fund (PLTFYARENG53); Institute of Solid-State Physics, University of Latvia has received funding from the European Union's Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-Teaming Phase 2 under grant agreement No. 739508, project CAMART2

IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by recessive mutations in the AIRE gene. The hallmark of the disease is the production of highly neutralizing autoantibodies against type I interferons and IL-22. Considering the importance of IL-22 in maintaining mucosal barrier integrity and shaping its microbial community, we sought to study potential changes in the oral cavity in this model of human IL-22 paucity. We found that besides known Th22 cell deficiency, APECED patients have significantly fewer circulating MAIT cells with potential IL-22 secreting capacity. Saliva samples from APECED patients revealed local inflammation, the presence of autoantibodies against IFN-α and IL-22, and alterations in the oral microbiota. Moreover, gene expression data of buccal biopsy samples suggested impaired antimicrobial response and cell proliferation, both of which are processes regulated by IL-22. Our data complement the knowledge gained from mouse models and support the concept of IL-22 being a critical homeostatic cytokine in human mucosal sites

Anticommensal Responses Are Associated with Regulatory T Cell Defect in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Patients

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p <0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti-IL-17 or -IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti-S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO(+) population (rho = 20.706; p <0.01). APECED patients also had decreased numbers of FOXP3(+) cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn's disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non-self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED.Peer reviewe

Dissolution of Silver Nanowires and Nanospheres Dictates Their Toxicity to Escherichia coli

Silver nanoparticles are extensively used in antibacterial applications. However, the mechanisms of their antibacterial action are not yet fully explored. We studied the solubility-driven toxicity of 100 × 6100 nm (mean primary diameter × length) silver nanowires (NWs) to recombinant bioluminescent Escherichia coli as a target representative of enteric pathogens. The bacteria were exposed to silver nanostructures in water to exclude the speciation-driven alterations. Spherical silver nanoparticles (83 nm mean primary size) were used as a control for the effect of NPs shape. Toxicity of both Ag NWs and spheres to E. coli was observed at similar nominal concentrations: the 4h EC50 values, calculated on the basis of inhibition of bacterial bioluminescence, were 0.42 ± 0.06 and 0.68 ± 0.01 mg Ag/L, respectively. Dissolution and bioavailability of Ag from NWs and nanospheres, analyzed with AAS or Ag-sensor bacteria, respectively, suggested that the toxic effects were caused by solubilized Ag + ions. Moreover, the antibacterial activities of Ag NWs suspension and its ultracentrifuged particle-free supernatant were equal. The latter indicated that the toxic effects of ∼80-100 nm Ag nanostructures to Escherichia coli were solely dependent on their dissolution and no shape-induced/related effects were observed. Yet, additional nanospecific effects could come into play in case of smaller nanosilver particles