Scandinavian Journal of Immunology最新文献

{"title":"Impact of gluten intake on clinical outcomes in patients with chronic inflammatory diseases initiating biologics: Secondary analysis of the prospective multicentre BELIEVE cohort study.","authors":"Laura Gregersen, Pernille Dyhre Jessen, Helene Wiencke Lund, Silja Hvid Overgaard, Zainab Hikmat, Torkell Ellingsen, Jens Kjeldsen, Andreas Kristian Pedersen, Sofie Ronja Petersen, Mohamad Jawhara, Anders Bathum Nexøe, Anette Bygum, Christian Lodberg Hvas, Jens Frederik Dahlerup, Frederik Olof Bergenheim, Henning Glerup, Rikke Holm Henriksen, Tanja Guldmann, Lone Hvid, Jacob Brodersen, Heidi Lausten Munk, Natalia Pedersen, Sanaz Saboori, Ole Haagen Nielsen, Berit Lillenthal Heitmann, Thorhallur Ingi Haldorsson, Robin Christensen, Vibeke Andersen","doi":"10.1111/sji.13409","DOIUrl":"https://doi.org/10.1111/sji.13409","url":null,"abstract":"<p><p>Chronic inflammatory diseases (CIDs) pose a growing healthcare challenge, with a substantial proportion of patients showing inadequate response to biological treatment. There is renewed interest in dietary changes to optimize treatment regimens, with a growing body of evidence suggesting beneficial effects with adherence to a gluten-free diet. This study compared the likelihood of achieving clinical response to biological treatment after 14-16 weeks in patients with CID with high versus low-to-medium gluten intake. Secondary outcomes of interest included changes in disease activity, health-related quality of life and C-reactive protein. The study was a multicentre prospective cohort of 193 participants with a CID diagnosis (i.e. Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis or Psoriasis) who initiated biological treatment between 2017 and 2020. Participants were stratified based on their habitual gluten intake: the upper 33.3% (high gluten intake) and the remaining 66.6% (low-to-medium gluten intake). The proportion of patients achieving clinical response to biological treatment after 14-16 weeks was compared using logistic regression models. The median gluten intake differed significantly between groups (12.5 g/day vs. 5.9 g/day, standardized mean difference = 1.399). In total, 108 (56%) achieved clinical response to treatment, with no difference between 35 (55%) in the high gluten group and 73 (57%) in the medium-to-low gluten group (OR = 0.96 [0.51-1.79], p = 0.897). No differences were found with secondary outcomes. In conclusion, this study found no association between gluten intake and response to biological treatment in patients with CID.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366400","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":"Tetraspanin32 (TSPAN32) is downregulated in rheumatoid arthritis: Evidence from animal models and patients.","authors":"Katia Mangano, Jose' Francisco Munoz-Valle, Claudia Azucena Palafox-Sánchez, Maria Cristina Petralia, Gian Marco Leone, Paolo Fagone, Ferdinando Nicoletti","doi":"10.1111/sji.13410","DOIUrl":"https://doi.org/10.1111/sji.13410","url":null,"abstract":"<p><p>This study aimed to investigate the role of TSPAN32, a member of the tetraspanin family, in rheumatoid arthritis (RA). The objective was to assess the expression levels of TSPAN32 in experimental RA models and in RA patient immune cells, exploring its potential as a regulatory factor in RA pathogenesis. The study employed adjuvant-induced arthritis in rats and collagen-induced arthritis (CIA) in mice as experimental models. Ex vivo analyses included evaluating TSPAN32 expression in immune cells at different stages of the disease. In silico data analysis involved examining transcriptomic datasets from drug-naïve and treated RA patients to correlate TSPAN32 expression with clinical parameters. TSPAN32 overexpression experiments in splenocytes from CIA mice aimed to demonstrate its functional impact on antigen-specific immune responses. The animal models revealed a significant downregulation of TSPAN32, particularly in synovial-infiltrating T cells. Also, TSPAN32 overexpression inhibited pro-inflammatory cytokine production in splenocytes. In RA patients, TSPAN32 was consistently downregulated in circulating and synovial-infiltrating T cells, as well as in CD8+ T cells, B cells and NK cells. Drug treatment did not significantly alter TSPAN32 levels. Negative correlations were observed between TSPAN32 expression and inflammatory markers (CRP, ESR) and clinical scores (SDAI) in RA patients. This study suggests that reduced TSPAN32 expression characterizes pathogenic T-cell populations in RA, highlighting its potential as biomarker for inflammation and disease activity. TSPAN32 may play a crucial role in shaping adaptive immune responses in RA, opening avenues for novel therapeutic strategies targeting this tetraspanin family member.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353022","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":"Somatic reversion in Wiskott-Aldrich syndrome: Case reports and mechanistic insights.","authors":"Rashmi Rikhi, Suprit Basu, Kanika Arora, Koon-Wing Chan, Ankur Kumar Jindal, Amit Rawat, Yu-Lung Lau, Deepti Suri","doi":"10.1111/sji.13408","DOIUrl":"https://doi.org/10.1111/sji.13408","url":null,"abstract":"<p><p>This report describes two brothers from India and a Chinese patient with somatic reversion of an inherited deleterious mutation in the WAS gene. Both the Indian siblings had inherited a single nucleotide deletion causing a frameshift mutation (c.1190del, p.Pro397Argfs*48) (variant 1: marked in blue) from the mother. Another variant (variant 2: marked in red), a 12-nucleotide deletion at position 1188-1199 (c.1188_1199del, p.P401_P404del) was also found, which resulted in restoration of the frame and subsequent rescue of the protein sequence. DNA sequencing from buccal mucosal cells revealed only the inherited variant (variant 1), while no reversion mutation was identified in the mucosal cells. Similarly, the Chinese patient was found to have a novel germline 14-base duplication (ACGAAAATGCTTGG) c.120_132 + 1dup (variant 1). This resulted in abolishment of the original splice junction coupled with the creation of a new junction 14 bases 3' and a frameshift mutation with predicted protein truncation p. Thr45Aspfs*. DNA from the patient's PBMC showed co-existence of wild-type and mutated sequences, but only the mutant was present in the buccal cells. Genomic and mRNA analysis of the isolated CD3+ T lymphocytes, CD3- mononuclear cells, and EBV-transformed B lymphocytes indicated that the reverant variant (germline variant was restored to wild-type sequence) were selectively found in CD3+ T lymphocytes.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294405","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":"No signs of mast cell involvement in long‐COVID: A case–control study","authors":"Ole Bernt Lenning, Grete Jonsson, Tore Grimstad, Emiel A. M. Janssen, Geir Sverre Braut, Frode Berven, Roald Omdal","doi":"10.1111/sji.13407","DOIUrl":"https://doi.org/10.1111/sji.13407","url":null,"abstract":"Long‐COVID caused by SARS‐CoV‐2 infection has significant and increasing effects on human health worldwide. Although a unifying molecular or biological explanation is lacking, several pathophysiological mechanisms have been proposed. Involvement of mast cells—evolutionary old “multipurpose” innate immune cells—was reported recently in studies of acute infection and post‐acute‐COVID‐19 syndrome. Mast cell activity has been suggested in long‐COVID. In this case–control study, we compared data from 24 individuals with long‐COVID (according to the NICE criteria) and 24 age‐ and sex‐matched healthy individuals with a history of SARS‐CoV‐2 infection without developing sequelae. Serum levels of the proteases beta‐tryptase (TPSB2) and carboxypeptidase (CPA3), which are mast cell specific, were measured using immunoassays. The values were compared between the two groups and correlated to measures of physical exertional intolerance. TPSB2 and CPA3 levels were median (range) 26.9 (2.0–1000) and 5.8 (1.5–14.0) ng/mL, respectively, in the long‐COVID group. The corresponding values in the control group were 10.9 (2.0–1000) (<jats:italic>p</jats:italic> = 0.93) and 5.3 (3.5–12.9) ng/mL (<jats:italic>p</jats:italic> = 0.82). No significant correlations between TPSB2 or CPA3 levels and scores on the ten physical subscales of SF‐36, 3.1–3.10 were revealed. We found no significant differences in the levels of mast cell activation markers TPSB2 and CPA3 between the long‐COVID and control groups and no correlations with proxy markers of exercise intolerance. Mast cell activation does not appear to be part of long‐term pathogenesis of long‐COVID, at least in the majority of patients.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256646","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":"Relevance of antigen‐induced IL‐6 and mitogen‐induced or spontaneous IFN‐γ secretions in whole blood cultures for detection of Mycobacterium tuberculosis infection and disease","authors":"Sudhir Sinha, Komal Singh, Fareha Umam, Prerna Kapoor, Amita Aggarwal","doi":"10.1111/sji.13406","DOIUrl":"https://doi.org/10.1111/sji.13406","url":null,"abstract":"For an effective control of tuberculosis (TB), there is a persistent need for biomarkers that can report true estimates of TB infection (TBI) and predict its progression towards active TB disease. We investigated whether the cell‐mediated immune responses to <jats:italic>Mycobacterium tuberculosis</jats:italic> (Mtb) antigens could provide such biomarkers. The study subjects (<jats:italic>n</jats:italic> = 174) comprised a cohort of smear‐positive, drug‐sensitive, HIV‐negative pulmonary TB patients (<jats:italic>n</jats:italic> = 54) and their household contacts (HC, <jats:italic>n</jats:italic> = 120). Whole blood cultures, in the presence or absence of Mtb antigens‐ membrane (MtM), purified protein derivative (PPD) and alpha‐crystallin (Acr), or the mitogen PHA were subjected to determinations, by flow cytometry, for T cell proliferative and, by ELISA, for IFN‐γ, TNF‐α, and IL‐6 cytokine responses. Additionally, serum levels of the three cytokines were also estimated. The strongest cell‐proliferative and cytokine responses were induced by MtM and IL‐6 was the most abundantly produced cytokine. While none of the responses induced by Mtb antigens or the serum cytokines levels could discriminate between TB and HC, the ex vivo cytokine responses induced by PHA or ‘spontaneously’ could apparently do so. The concentrations of IFN‐γ induced by PHA in TB blood cultures were significantly lower than in HC cultures (AUC = 0.72). Conversely, the spontaneous IFN‐γ or TNF‐α secretions in TB cultures were significantly higher than in HC cultures (AUC = 0.66). Our results suggest that IL‐6 responses to MtM could be a sensitive indicator of TBI, and low levels of PHA‐induced or high levels of spontaneous IFN‐γ secretions in HC blood cultures may indicate a progressive infection.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256643","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":"Patho‐immunological mechanisms of atopic dermatitis: The role of the three major human microbiomes","authors":"Zhaosen Zhou, Jing Yang, Qin Liu, Jing Gao, Wenting Ji","doi":"10.1111/sji.13403","DOIUrl":"https://doi.org/10.1111/sji.13403","url":null,"abstract":"Atopic dermatitis (AD) is a genetically predisposed allergic inflammatory dermatosis with chronic, pruritic, and recurrent features. Patients with AD have dry and itchy skin, often accompanied by chronic eczematous lesions, allergic rhinitis, or asthma, which has a considerable impact on their daily lives. With advances in genome sequencing technology, it has been demonstrated that microorganisms are involved in this disease, and the microorganisms associated with AD are attracting considerable research attention. An increasing number of studies conducted in recent years have demonstrated that an imbalanced microbiome in AD patients has substantial impact on disease prognosis, and the causes are closely tied to various immune mechanisms. However, the involvement of microorganisms in the pathogenesis of AD remains poorly understood. In this paper, we review the advances in research on the immunological mechanisms of the skin microbiome, intestinal microbiome, and lung microbiome that are related to AD prognosis and immunotherapy protocols. It is hoped that this approach will lay the foundation for exploring the pathogenesis of and emerging treatments for AD.","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256684","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":"Mucosal-associated invariant T cells modulate innate immune cells and inhibit colon cancer growth.","authors":"Olivia J Cheng, Eric J Lebish, Owen Jensen, Damian Jacenik, Shubhanshi Trivedi, Jackson G Cacioppo, Jeffrey Aubé, Ellen J Beswick, Daniel T Leung","doi":"10.1111/sji.13391","DOIUrl":"10.1111/sji.13391","url":null,"abstract":"<p><p>Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions and have potentials for use as adoptive cell therapy. However, studies into their anti-cancer activity, including their role in colon cancer, are limited. Using an animal model of colon cancer, we showed that peritumoral injection of in vivo-expanded MAIT cells into RAG1^-/- mice with MC38-derived tumours inhibits tumour growth compared to control. Multiplex cytokine analyses showed that tumours from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting a potential association between eosinophil recruitment and tumour inhibition. In a human peripheral leukocyte co-culture model, we showed that leukocytes stimulated with MAIT ligand showed an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. In conclusion, we showed that MAIT cells have a protective role in a murine colon cancer model, associated with modulation of the immune response to cancer, potentially involving eosinophil-associated mechanisms. Our results highlight the potential of MAIT cells for non-donor restricted colon cancer immunotherapy.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PLA2G2D promotes immune escape in non-small cell lung cancer by regulating T cell immune function through PD-L1-expressing extracellular vesicles.","authors":"Hui Jing, Xubo Cao, Ke Li, Yuanyuan Liu, Meng Meng, Shuan Liu, Mengjie Ye, Jinghao Zhang, Yanmin Wu","doi":"10.1111/sji.13393","DOIUrl":"10.1111/sji.13393","url":null,"abstract":"<p><p>It is urgent to explore factors affecting immunotherapy efficacy to benefit non-small cell lung cancer (NSCLC) patient survival. Bioinformatics predicted genes associated with programmed cell death ligand 1 (PD-L1) expression and analysed phospholipase A2 group IID (PLA2G2D) expression in NSCLC. BODIPY 493/503 dye staining and kits detected lipids, triglycerides, and phospholipids in H1299 cells, respectively. Extracellular vesicles (EVs) were extracted for morphology and size assessment using electron microscopy. Western blot assayed CD9, CD63, HSP90, EVs-PD-L1, PD-L1, and PLA2G2D expression. CCK-8, LDH, and ELISA tested proliferation and toxicity of CD8⁺ T cells, interleukin-2, and interferon-gamma secretion, respectively. PLA2G2D, PD-L1, and Ki67 expression was detected by immunohistochemistry. Immunofluorescence assayed PLA2G2D localisation and CD8⁺ T cell content. Flow cytometry assessed PD-L1 and CD8 expression. In NSCLC, upregulated EVs-PD-L1 and clinical characteristics showed a strong correlation. H1299 cells with overexpression PD-L1 significantly reduced proliferation, toxicity of CD8⁺ T cells, and interleukin-2 and interferon-gamma levels. Bioinformatics revealed positive correlations between PLA2G2D and overexpressed PD-L1. PLA2G2D was expressed in macrophages and dendritic cells in NSCLC tissue. Overexpression PLA2G2D (oe-PLA2G2D) increased lipids, triglycerides, and phospholipids contents in H1299 cells. oe-PLA2G2D significantly reduced proliferation, toxicity of CD8⁺ T cells, and interleukin-2 and interferon-gamma levels. si-PD-L1 restored inhibition of oe-PLA2G2D on CD8⁺ T cells. oe-PLA2G2D significantly increased mice tumour volume and weight, upregulated expression of blood EVs-PD-L1 and tissue PD-L1, PLA2G2D, Ki67, and decreased CD8⁺ T cell content. PLA2G2D facilitated immune escape in NSCLC by regulating CD8⁺ T cell immune function by upregulating EVs-PD-L1.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459061","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":"Effects of smoking on clinical treatment outcomes amongst patients with chronic inflammatory diseases initiating biologics: secondary analyses of the prospective BELIEVE cohort study.","authors":"Maja Graves Rosenkilde Larsen, Silja Hvid Overgaard, Sofie Ronja Petersen, Karen Mai Møllegaard, Heidi Lausten Munk, Anders Bathum Nexøe, Henning Glerup, Tanja Guldmann, Natalia Pedersen, Sanaz Saboori, Jens Frederik Dahlerup, Christian Lodberg Hvas, Karina Winther Andersen, Mohamad Jawhara, Ole Haagen Nielsen, Fredrik Olof Bergenheim, Jacob Broder Brodersen, Anette Bygum, Torkell Ellingsen, Jens Kjeldsen, Robin Christensen, Vibeke Andersen","doi":"10.1111/sji.13395","DOIUrl":"10.1111/sji.13395","url":null,"abstract":"<p><p>The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a \"crude\" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a \"crude\" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the \"crude\" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555450","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":"Glycoxidation of mammalian whole histone generates highly immunogenic aggregates: Sera of SLE patients contain autoantibodies against aggregates.","authors":"Shireen Naaz Islam, Zarina Arif, Asim Badar, Moinuddin, Md Asad Khan, Khursheed Alam","doi":"10.1111/sji.13389","DOIUrl":"10.1111/sji.13389","url":null,"abstract":"<p><p>Non-enzymatic glycation and oxidation of self-proteins, causing formation and accumulation of advanced glycation end products (AGEs), have been reported in an array of pathologies, including systemic lupus erythematosus (SLE). Such modifications may generate neo-epitopes, break immunological tolerance, and induce antibody response. In this study, we have first analysed the structural modifications of whole histone in the presence of deoxyribose followed by oxidation with hydroxyl radicals. Changes in the secondary and tertiary structure of the whole histone were determined by spectroscopic techniques and biochemical assays. Fluorescence spectroscopy and UPLC-MS showed the generation of AGEs such as carboxymethyl lysine and pentosidine, while DLS and TEM indicated the presence of amorphous AGE-aggregates. Moreover, rabbits immunized with these histone-AGEs exhibited enhanced immunogenicity and ELISA and western immunoblot of IgG antibodies from SLE patients' sera showed a significantly higher specificity towards modified histone-AGEs than the native histone.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180684","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}