{"title":"Pimecrolimus protects <scp>neuron‐like SH‐SY5Y</scp> cells against anti‐inflammatory and anti‐oxidant effects of both microglial secretome and hydrogen peroxide","authors":"Fatma Gonca Kocanci, Azize Yasemin Goksu Erol, Fatma Yildiz, Hamiyet Eciroglu","doi":"10.1111/sji.13328","DOIUrl":"https://doi.org/10.1111/sji.13328","url":null,"abstract":"Abstract Calcineurin inhibitors have been found to exhibit a preventive role against neuroinflammation, which represents a crucial underlying mechanism in neurodegenerative diseases (ND). Additionally, they possess suppressive effects on the activation of apoptotic pathways, which constitute another mechanism underlying such diseases. Given that pimecrolimus, a calcineurin inhibitor, impedes the synthesis of pro‐inflammatory cytokines, such as interleukin (IL)‐2, IL‐4, and IL‐10, and influences apoptotic processes, it is noteworthy to test its potential neuroprotective properties. Thus, the objective of this investigation was to assess the potential protective effects of pimecrolimus against the degenerative consequences of both microglial secretomes and hydrogen peroxide (H 2 O 2 ), an oxidant agent. The survival rates of HMC3 microglia cells, neuron‐like differentiated SH‐SY5Y (d‐SH‐SY5Y) cells, and their co‐culture were determined using the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) method. Furthermore, the levels of pro‐inflammatory cytokines IL‐1β and IL‐6, and anti‐inflammatory cytokine IL‐10 were measured using ELISA kits, besides total antioxidant and oxidant capacities in conditioned media of cells. Additionally, the effect of pimecrolimus on neurite length in these cell groups was evaluated through morphological observations. This study revealed, for the first time, that pimecrolimus exerts preventive effects on neurodegenerative processes by virtue of its anti‐inflammatory and ‐antioxidant activities. It holds promise as a potential treatment option for ND.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135980874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lijun Tian, Junxian Xu, Cong Chen, Jinfeng Lin, Linling Ju, Lin Chen, Yufeng Zhang, Xudong Han, Lijun Liu
{"title":"HLA-DR<sup>+</sup> mucosal-associated invariant T cells predict poor prognosis in patients with sepsis: A prospective observational study.","authors":"Lijun Tian, Junxian Xu, Cong Chen, Jinfeng Lin, Linling Ju, Lin Chen, Yufeng Zhang, Xudong Han, Lijun Liu","doi":"10.1111/sji.13286","DOIUrl":"10.1111/sji.13286","url":null,"abstract":"<p><p>Mucosal-associated invariant T (MAIT) cells are important in antibacterial immune responses; however, during sepsis, they are few in number and exhibit highly activated phenotypes. The relationship between MAIT cells in peripheral blood and the prognosis of sepsis is not well understood. Thus, this study aimed to examine the levels and phenotypes of MAIT cells in early sepsis, evaluate their clinical relevance, and investigate their association with patient prognosis. This prospective observational study enrolled 72 septic patients defined according to the Sepsis 3.0 criteria and 21 healthy controls matched for age and sex. Their peripheral blood samples were used to assay the expression of immune activation (CD69 and HLA-DR) and immune checkpoint (PD-1 and PD-L1) markers on MAIT cells. The systemic inflammatory response syndrome, acute physiology and chronic health evaluation (APACHE) II, and sequential organ failure assessment scores were recorded. Subsequently, the association between MAIT cell characteristics and clinical indicators was assessed using Spearman's rank correlation analysis, and binary logistic regression analysis with a forward stepwise approach assessed independent risk factors for 28-day mortality. We noted a decrease in the percentage of MAIT cells in the patients' peripheral blood, which exhibited an activated phenotype. Besides, HLA-DR<sup>+</sup> MAIT cell percentage and the APACHE II score were independently associated with the 28-day mortality and, in combination, were the best indicators of mortality. Thus, the percentage of HLA-DR<sup>+</sup> MAIT cells in early sepsis serves as a novel prognostic biomarker for predicting mortality and improves the predictive capacity of the APACHE II score.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"98 3","pages":"e13286"},"PeriodicalIF":3.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9947938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relapsing/remitting multiple sclerosis: A speculative model and its implications for a novel treatment","authors":"Peter Bretscher","doi":"10.1111/sji.13325","DOIUrl":"https://doi.org/10.1111/sji.13325","url":null,"abstract":"Abstract The clinical pattern in relapsing/remitting multiple sclerosis may be accounted for if an autoreactive immune response can transition back and forth between inflammatory, pathogenic, and non‐inflammatory, non‐pathogenic modes. Such ‘back‐and‐forth’ immune responses are rare. I speculate how such back‐and‐forth immune responses may arise. Understanding the nature of these different modes, and what controls their mutual transition, may help in designing strategies to favour the nonpathogenic mode, thus constituting treatment. Antigen dose is known to be critical in determining the class/subclass of primary immune responses. Observations have led us to suggest the level of antigen also similarly influences the class/subclass of on‐going immune responses. I propose the relapsing, inflammatory and the remitting modes are respectively sustained by relatively low and high amounts of the responsible autoantigens, as is the case, for example, for Th1 and Th2 responses to foreign antigens. In addition, I propose more self‐antigens are released during an inflammatory than during a remitting mode. The decrease in the amount of antigen released, as the response transitions from an inflammatory to a remitting mode, results in time in a decreased level of antigen and so the response again evolves towards the inflammatory mode. The inflammatory mode then leads to an increased release of antigen and so, in time, to remission. This model thus explains the transition between different modes. I outline non‐invasive, testable predictions of the hypothesis. If confirmed, it may be ethical to examine whether the non‐inflammatory mode can be sustained by administering myelin antigens during the remitting phase.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"59 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135875777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joshua M Mutiso, Ciriaka M Gitonga, Michael M Gicheru
{"title":"TGF-β levels significantly increases in patients with stage III and IV breast cancer and can be explored as a target for tumour diagnosis and staging.","authors":"Joshua M Mutiso, Ciriaka M Gitonga, Michael M Gicheru","doi":"10.1111/sji.13280","DOIUrl":"10.1111/sji.13280","url":null,"abstract":"","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"98 2","pages":"e13280"},"PeriodicalIF":3.7,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9789273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How the initial discovery of modified RNA enabled evasion of innate immune responses and facilitated the development of RNA therapeutics.","authors":"Mouldy Sioud","doi":"10.1111/sji.13282","DOIUrl":"https://doi.org/10.1111/sji.13282","url":null,"abstract":"<p><p>Besides being the physical link between DNA and proteins, RNAs play several other key roles, including RNA catalysis and gene regulation. Recent advances in the design of lipid nanoparticles have facilitated the development of RNA-based therapeutics. However, chemically and in vitro transcribed RNAs can activate innate immunity, leading to the production of proinflammatory cytokines and interferons, a response similar to the one induced by viral infections. Since these responses are undesirable for certain therapeutic applications, it is important to develop ways to block the sensing of exogenous RNAs by immune cells, such as monocytes, macrophages and dendritic cells. Fortunately, RNA sensing can be blocked by chemical modifications of certain nucleotides, particularly uridine, a finding that has facilitated the development of RNA-based therapeutics such as small interfering RNAs and mRNA vaccines. Here, I provide a backstory on how improved understanding of RNA sensing by innate immunity can be applied to develop more effective RNA therapeutics.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"98 1","pages":"e13282"},"PeriodicalIF":3.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9630436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vijaya Gowri, Akshaya Chougule, Maya Gupta, Prasad Taur, Vaishnavi V Iyengar, Meena Sivasankaran, Deenadayalan Munirathnam, Sushma Krishna, Umair A Bargir, Aparna Dalvi, Priyanka Setia, Neha Jodhawat, Shweta Shinde, Shakuntala S Prabhu, Minnie Bodhanwala, Manisha R Madkaikar, Mukesh M Desai
{"title":"Clinical, immunological and molecular findings of patients with DOCK-8 deficiency from India.","authors":"Vijaya Gowri, Akshaya Chougule, Maya Gupta, Prasad Taur, Vaishnavi V Iyengar, Meena Sivasankaran, Deenadayalan Munirathnam, Sushma Krishna, Umair A Bargir, Aparna Dalvi, Priyanka Setia, Neha Jodhawat, Shweta Shinde, Shakuntala S Prabhu, Minnie Bodhanwala, Manisha R Madkaikar, Mukesh M Desai","doi":"10.1111/sji.13276","DOIUrl":"https://doi.org/10.1111/sji.13276","url":null,"abstract":"<p><p>DOCK8 deficiency affects various cell subsets belonging to both the innate and adaptive immune systems. Clinical diagnosis is challenging, as many cases present with severe atopic dermatitis as the only initial manifestation. Though flow cytometry helps in the presumptive diagnosis of DOCK8-deficient patients by evaluating their DOCK8 protein expression, it requires subsequent confirmation by molecular genetic analysis. Currently, haematopoietic stem cell transplantation (HSCT) is the only curative treatment option available for these patients. There is a paucity of data from India on the clinical diversity and molecular spectrum of DOCK8 deficiency. In the present study, we report the clinical, immunological and molecular findings of 17 DOCK8-deficient patients from India diagnosed over the last 5 years.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"98 1","pages":"e13276"},"PeriodicalIF":3.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9621589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Magne Kristoffer Fagerhol, Nina Haagenrud Schultz, Mohammad Reza Mirlashari, Markus Karl Hermann Wiedmann, Lise Sofie Haug Nissen-Meyer, Arne Vasli Lund Søraas, Geir Hetland
{"title":"DNase analysed by a novel competitive assay in patients with complications after ChAdOx1 nCoV-19 vaccination and in normal unvaccinated blood donors.","authors":"Magne Kristoffer Fagerhol, Nina Haagenrud Schultz, Mohammad Reza Mirlashari, Markus Karl Hermann Wiedmann, Lise Sofie Haug Nissen-Meyer, Arne Vasli Lund Søraas, Geir Hetland","doi":"10.1111/sji.13274","DOIUrl":"10.1111/sji.13274","url":null,"abstract":"<p><p>Increased levels of neutrophil extracellular traps (NETs) have been detected in individuals with vaccine complications after the ChAdOx1 nCov vaccine with a correlation between the severity of vaccine side effects and the level of NETosis. DNases may disrupt NETs by degrading their content of DNA, and a balance has been reported between NETs and DNases. Because of this and since the inflammatory marker NETs may be used as a confirmatory test in diagnosing VITT, it is of interest to monitor levels of DNase in patients with increased NETs levels. The current novel rapid DNase ELISA was tested in blood samples of patients with known increased levels of NETs with or without VITT after ChAdOx1 nCoV-19 vaccination. DNase levels in VITT patients were significantly increased compared with normal unvaccinated blood donors and compared with patients with post-vaccination symptoms but not VITT. However, since EDTA was found to inhibit DNase, serum and not EDTA-plasma samples should be applied for DNase testing. The novel DNase assay may serve as a supplementary test to the NETs test when analysing samples from patients with suspected increased NETs levels.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"98 1","pages":"e13274"},"PeriodicalIF":3.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10551214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Luminex Crossmatch in kidney transplantation.","authors":"Radouan Fadi Ameur, Lilya Meriem Berkani, Brahim Belaid, Khadidja Habchi, Messaoud Saidani, Reda Djidjik","doi":"10.1111/sji.13279","DOIUrl":"https://doi.org/10.1111/sji.13279","url":null,"abstract":"<p><p>The introduction of the Luminex Crossmatch assay (LumXm) which uses Luminex bead technology, consists of extracting the donor's Human Leukocyte Antigen (HLA) molecules from their lymphocytes, and binding them to fluorescent beads that are put in contact with recipient's serum. HLA donor-specific antibodies (DSA) are detected using a fluorescent conjugate. The goal of our study is to determine the benefits of using LumXm in a renal transplantation algorithm. We tested 78 recipients' sera using the LumXm, and the results were compared with the Luminex single antigen bead assay (SAB) for all sera, as well as the Flow Cytometry Crossmatch (FCXM) for 46 sera. We compared our results with those of SAB using 3 cutoffs, the first being the manufacturer's criteria where sensitivity and specificity were at 62.5% and 91.3% respectively for HLA class 1, and 88.5% and 50.0% respectively for HLA class 2. When using the third cutoff criteria (≥2 Adjusted values + MFI [Mean fluorescence intensity] >500 + Neg MFI < 500), the sensitivity increased to 69.0% for HLA class 1 and decreased to 84.0% for HLA class 2, while the specificity increased for HLA class 1 and 2. When comparing with FCXM, the 3 assays agreed in 55.8% of results for class 1 and 2 alike. However, major discrepancies were found for two groups in HLA class 1 and one in HLA class 2. The LumXm when used with other techniques to overcome its' weak points, can provide an interesting insight into the patient's HLA-DSA profile.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"98 1","pages":"e13279"},"PeriodicalIF":3.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9630440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Florian G Scurt, Verena Hirschfeld, Leon Schubert, Peter R Mertens, Christos Chatzikyrkou
{"title":"Monitoring disease activity in antineutrophil antibody-associated vasculitis.","authors":"Florian G Scurt, Verena Hirschfeld, Leon Schubert, Peter R Mertens, Christos Chatzikyrkou","doi":"10.1111/sji.13284","DOIUrl":"https://doi.org/10.1111/sji.13284","url":null,"abstract":"<p><p>Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises a group of multisystem disorders with alternating periods of relapse and remission. Beyond that, a smouldering progress during apparently clinically silent phases often develops. AAVs are subgrouped in microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and renal limited vasculitis (RLV). ANCA are hallmark of this disease entity, although they are not always present. Despite the simplification of treatment, fundamental aspects concerning assessment of its efficacy and its adaptation to encountered complications or to the relapsing/remitting/subclinical disease course remain still unknown. Through the advances in pathogenesis and pathophysiology of AAV a reliable biomarker-based monitoring and treatment algorithm has not been established and disease management follows not infrequently a \"trial and error\" approach. Here, we overviewed the most interesting biomarkers reported so far.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"98 1","pages":"e13284"},"PeriodicalIF":3.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9683575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Simultaneous neutralization of TGF-β and IL-6 attenuates Staphylococcus aureus-induced arthritic inflammation through differential modulation of splenic and synovial macrophages.","authors":"Rituparna Ghosh, Rajen Dey, Ritasha Sawoo, Biswadev Bishayi","doi":"10.1111/sji.13252","DOIUrl":"https://doi.org/10.1111/sji.13252","url":null,"abstract":"<p><p>Septic arthritis is a joint disease caused by Staphylococcus aureus. Different macrophage populations contribute in various ways to control blood-borne infections and induce inflammatory responses. Macrophage tissue-resident niche is necessary for the suppression of chronic inflammation and may contribute to the pathogenesis of septic arthritis. Thus, to obtain a resolution of the disease and restoration of synovial homeostasis, it needs the activation of macrophages that further regulate the inflammatory consequences. The aim of this study was to find out the mechanism by which neutralization of transforming growth factor-beta (TGF-β) and/or interleukin (IL)-6 after induction of septic arthritis could alter the specific macrophage responses in spleen and synovial joints via different cytokines (osteoprotegerin (OPG), osteopontin (OPN), IL-10, IL-12 and CXCL8) cross-talking, and how the response could be modulated by reactive oxygen species vs antioxidant enzyme activities. Dual neutralization of TGF-β and IL-6 is notably effective in eliciting splenic and synovial tissue-resident macrophage responses. Synovial macrophage-derived IL-10 can elicit protection against septic arthritis via regulating receptor-activated nuclear factor Kappa-B ligand (RANKL)/OPG interaction. They also reduced oxidative stress by increasing the activity of antioxidant enzymes including SOD and catalase. Histopathological analysis revealed that dual neutralization of TGF-β and IL-6 prevented bone destruction and osteoclastic activity in septic arthritis by promoting the differential functional response of the splenic and synovial macrophages. Additionally, the macrophage-derived IL-10 can elicit protection against S. aureus-induced septic arthritis via regulating RANKL/OPG interaction. Further studies on STAT3 and STAT4 are needed for the understanding of such cross-talking in resident macrophages of arthritic mice.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"97 6","pages":"e13252"},"PeriodicalIF":3.7,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9534306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}