Ludmiła Szewczak, Maja Machcińska, Magdalena Kierasińska, Urszula Zawadzka-Więch, Marta Maruszewska-Cheruiyot, Paweł Majewski, Anna Karlińska, Rafał Rola, Katarzyna Donskow-Łysoniewska
{"title":"Expression of STAT- and T-cell-related genes in women with first-line treatment of relapsing-remitting multiple sclerosis.","authors":"Ludmiła Szewczak, Maja Machcińska, Magdalena Kierasińska, Urszula Zawadzka-Więch, Marta Maruszewska-Cheruiyot, Paweł Majewski, Anna Karlińska, Rafał Rola, Katarzyna Donskow-Łysoniewska","doi":"10.1111/sji.13424","DOIUrl":"10.1111/sji.13424","url":null,"abstract":"<p><p>Relapsing-remitting multiple sclerosis is associated with changes in Jak/STAT pathways in immune cells, but the influence of disease-modifying drugs on these pathways is poorly understood. The aim of this study was to evaluate the impact of first-line disease-modifying drugs used in treatment of RRMS on expression of the STAT pathway and T-cell-related genes in the blood and on serum concentrations of sgp130 and TGF-β1 in women, as well as on the level of phosphorylated STAT3 and STAT5 proteins in T cells of untreated patients and heathy controls. Expression of STAT1, STAT3, STAT5A, STAT5B, SOCS1, SOCS3, FOXP3, IKZF2, RORC and ICOS genes in the blood of untreated RRMS patients, in the blood of patients treated with interferon-β, glatiramer acetate, dimethyl fumarate or teriflunomide and in the blood of healthy controls was evaluated using droplet digital PCR. Serum concentrations of sgp130 and TGF-β1 were evaluated by ELISA. Phosphorylated STAT3 and STAT5 protein levels in T cells were evaluated by flow cytometry. STAT3 gene expression was significantly higher in untreated patients than in healthy control, but the level of phosphorylated STAT3 in T cells was significantly lower. Patients treated with interferon-β or dimethyl fumarate had significantly lower STAT3 gene expression. Patients treated with teriflunomide had higher STAT1 gene expression, than untreated patients. Patients treated with dimethyl fumarate also had significantly lower RORC gene expression than untreated patients. The study shows the impact of drugs used in first-line treatment of relapsing-remitting multiple sclerosis on expression of STAT and T-cell-related genes.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13424"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639700","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}
Yan Feng, Zhishou Zhang, Hui Huangfu, Haiyang Han, Bailing Xie, Shuo Song, Tao Liu, Yunfang An, Pingchang Yang
{"title":"Adjuvant alum regulates the eIF2a-GATA3 axis in CD4<sup>+</sup> T cells to influence allergen immunotherapy.","authors":"Yan Feng, Zhishou Zhang, Hui Huangfu, Haiyang Han, Bailing Xie, Shuo Song, Tao Liu, Yunfang An, Pingchang Yang","doi":"10.1111/sji.13419","DOIUrl":"10.1111/sji.13419","url":null,"abstract":"<p><p>Allergen-specific immunotherapy (AIT) is an aetiology-targeting therapy for allergic diseases. The therapeutic mechanism of AIT is not fully understood yet. Endoplasmic reticulum stress is associated with the pathogenesis of allergic disorders. This study aims to elucidate the effects of AIT on suppressing allergic response through regulating endoplasmic reticulum stress. In this study, patients with perennial allergic rhinitis were recruited. AIT was conducted for the patients. An allergic rhinitis (AR) mouse model was established with mite extracts as allergens. We found that AIT modulated the endoplasmic reticulum stress status in peripheral CD4<sup>+</sup> T cells in patients with allergic rhinitis. The intensity of endoplasmic reticulum stress associated the PERK (protein kinase RNA-like endoplasmic reticulum kinase)-eIF2a (eukaryotic translation initiation factor 2a) axis in CD4<sup>+</sup> T cells was upregulated by AIT, which was closely associated with the improvement in allergic rhinitis response after AIT. eIF2a interacted with GATA3 to downregulate the IL4 gene transcription in CD4<sup>+</sup> T cells. High doses of aluminium hydroxide (alum) in AIT vaccines enhanced the activity of XBP1 to suppress eIF2a in CD4<sup>+</sup> T cells. AIT containing a low dose of alum effectively mitigated the experimental allergic rhinitis, while the AIT without alum or a high dose of alum exacerbated the experimental allergic rhinitis. In conclusion, the alum adjuvant in allergen vaccines can regulate the activity of eIF2a to regulate the expression of Th2 cytokines in CD4<sup>+</sup> T cells. Manipulating the alum dose in AIT vaccines has the potential to enhance the therapeutic effects of AIT.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13419"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676786","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}
Çağrı Şakalar, Büşra Kurt, Sedat Sezen, Savaş Kaya
{"title":"Production of novel peptide-targeting antibodies for anti-Müllerian hormone receptor 2 and induction of cytotoxicity in ovarian cancer cells.","authors":"Çağrı Şakalar, Büşra Kurt, Sedat Sezen, Savaş Kaya","doi":"10.1111/sji.13426","DOIUrl":"10.1111/sji.13426","url":null,"abstract":"<p><p>Ovarian cancer is generally diagnosed at late stages. Monoclonal antibodies (MAbs) targeting antigens in ovarian cancer are used in the clinic. Anti-Müllerian hormone receptor type 2 (AMHR2) is a receptor highly expressed in ovarian cancer and it is a potential target antigen for immunotherapy. Extracellular domain of AMHR2 was analysed in terms of 3D structure and physicochemical properties, and 3 peptide sequences (Peptides 1, 7 and 11) were determined as targets. MAb production protocol was performed, and 6 MAb clones showing high affinity for peptides were obtained. P3B1, P10A10, P10B6 and P2A6 clones were for peptide 11 (P11), P2C9 was for P7, and P6C5 was for P1. Antibody isotype of P2A6 was IgG2a and the others were of IgG1 isotype. MAb binding to the native recombinant protein (AMHR2-Fc) was analysed by enzyme-linked immunosorbent assay (ELISA) and MAb binding to AMHR2 expressed by SKOV-3 ovarian cancer cells was analysed by western blot and immunofluorescent staining. P3B1 showed strong, P10A10, P10B6 and P2C9 showed medium affinity for the native protein (AMHR2-Fc). P3B1 and P2C9 showed strong binding in western blot analysis. Clones showed moderate binding in immunoflorescent staining. A complement dependent cytotoxicity (CDC) experiment was conducted using MAbs and transfected SKOV-3 cells. P3B1 induced a significant CDC. Variable regions of P3B1 MAb were sequenced. In conclusion, MAbs for three different regions of AMHR2 were produced. One clone was shown to induce cytotoxicity in ovarian cancer cells and its sequence was determined for future use as a humanised therapeutic MAb.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13426"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710785","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}
Kittikorn Wangriatisak, Charlotte de Vries, Ravi Kumar Sharma, Wenqi Huang, Caroline Grönwall, Prapaporn Pisitkun, Iva Gunnarsson, Vivianne Malmström, Patchanee Chootong, Francesca Faustini
{"title":"Association between peripheral activated naive and double negative 2 B-cell subsets and clinical parameters in lupus nephritis patients.","authors":"Kittikorn Wangriatisak, Charlotte de Vries, Ravi Kumar Sharma, Wenqi Huang, Caroline Grönwall, Prapaporn Pisitkun, Iva Gunnarsson, Vivianne Malmström, Patchanee Chootong, Francesca Faustini","doi":"10.1111/sji.13427","DOIUrl":"10.1111/sji.13427","url":null,"abstract":"<p><p>Altered composition of B-cell compartments is a known feature in patients with systemic lupus erythematosus (SLE). However, deep characterisation of B-cell subsets and their relation to clinical manifestations and disease activity in patients is limited. In this study, we analysed peripheral B-cell subsets phenotype in SLE (n = 35) and healthy controls (HCs, n = 15) by spectral flow cytometry. Disease activity was stratified as inactive (SLEDAI-2 K score 0, n = 2), mild (SLEDAI-2 K score 1-5, n = 12), moderate (SLEDAI-2 K score 6-10, n = 6) or high (SLEDAI-2 K > 10, n = 15). An elevated proportion of activated naive (aNAV), double negative 2 (DN2) and plasmablasts (PB) was observed in patients with high disease activity, compared to other groups of patients and HCs. An upregulation of BTLA was found on both aNAV and DN2 and shifted to lower levels with increasing disease activity. In lupus nephritis (LN) patients (n = 21), aNAV B-cells were especially expanded and positively correlated with DN2 (r = 0.5, p = 0.019) and PB (r = 0.43, p = 0.048). Also, correlation was observed between DN2 and PB (r = 0.6, p = 0.003). Moreover, aNAV frequencies positively correlated with SLEDAI-2 K score, and negatively with the complement fractions C3 and C4. Further, aNAV, DN2 and PB were more expanded in association with positive anti-dsDNA antibodies, rather than other antibody specificities (anti-Sm). These data suggest roles of extrafollicular B cells as key players in disease development of LN. Their association with presence of anti-dsDNA antibodies may indicate their value as candidate biomarkers of kidney involvement in SLE.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13427"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732192","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}
Katia Mangano, Jose' Francisco Munoz-Valle, Claudia Azucena Palafox-Sánchez, Maria Cristina Petralia, Gian Marco Leone, Paolo Fagone, Ferdinando Nicoletti
{"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":"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":" ","pages":"e13410"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","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}
Zhao Wang, Khawar Ali Shahzad, Xuran Li, Boyu Cai, Maoxiang Xu, Jiaojiao Li, Fei Tan
{"title":"Immunomodulatory effect of mesenchymal stem cells-derived extracellular vesicles to modulate the regulatory T cells and Th1/Th2 imbalance in peripheral blood mononuclear cells of patients with allergic rhinitis.","authors":"Zhao Wang, Khawar Ali Shahzad, Xuran Li, Boyu Cai, Maoxiang Xu, Jiaojiao Li, Fei Tan","doi":"10.1111/sji.13416","DOIUrl":"10.1111/sji.13416","url":null,"abstract":"<p><p>Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown promising immunomodulatory capabilities for a variety of clinical conditions. However, the potential regulatory mechanisms of MSC-EVs in allergic rhinitis (AR) remain unexplored. The present study was designed to investigate the immunomodulatory effect of MSC-EVs in patients with AR. Peripheral blood mononuclear cells (PBMCs) were isolated from AR patients. The number of peripheral CD4<sup>+</sup>Foxp3<sup>+</sup>IL-17<sup>+</sup>, CD4<sup>+</sup>Foxp3<sup>+</sup>IL-17<sup>-</sup> and CD4<sup>+</sup>Foxp3<sup>-</sup>IL-17<sup>+</sup> T cells in healthy controls and AR patients were evaluated using flow cytometry. Therapeutic effect of MSC-EVs was determined by detecting IFN-γ, IL-4, IL-17 and IL-10 cytokines in supernatant by ELISA and flow cytometry. The mean fluorescence intensity (MFI) was calculated in PBMCs for IL-10, IL-17 and TGF-β on T cells after MSC-EVs treatment. Bioinformatic analysis of microRNA was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. CD4<sup>+</sup>Foxp3<sup>+</sup>IL-17<sup>+</sup> T cells expression in PBMCs was higher in the AR group and the balance of Treg/Th17 was tilted towards Th17 cells. Supernatant from AR patients revealed that MSC-EVs treatment upregulated IL-10 and IFN-γ, and downregulated IL-4 and IL-17. EVs treatment effectively re-established Th1(CD4<sup>+</sup>IFN-γ<sup>+</sup>cells)/Th2(CD4<sup>+</sup>IL-4<sup>+</sup>cells) balance, reduced CD4<sup>+</sup>IL-17<sup>+</sup> and increased CD4<sup>+</sup>IL-10<sup>+</sup> and CD4<sup>+</sup>TGF-β<sup>+</sup> cells. The MFI of IL-10 and TGF-β in CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>-</sup> T cells were higher, whereas lower levels of IL-17 were observed. Bioinformatic analysis revealed that the TGF-β, Wnt signalling pathways and STAT5 transcription factor might mechanistically support the immunomodulatory effect of MSC-EVs. This study presents the immunomodulatory effect of MSC-EVs in PBMCs from AR patients. The results provide a new therapeutic strategy for AR.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13416"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547139","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}
Julia Maroto-García, Minerva Mañez, Ana Martínez-Escribano, Ahlam Hachmaoui-Ridaoui, Carmen Ortiz, Carmen Ábalos-García, Inmaculada Gónzález, Ángela García de la Torre, Maximiliano Ruiz-Galdón
{"title":"A sex-dependent algorithm including kappa free light chain for multiple sclerosis diagnosis.","authors":"Julia Maroto-García, Minerva Mañez, Ana Martínez-Escribano, Ahlam Hachmaoui-Ridaoui, Carmen Ortiz, Carmen Ábalos-García, Inmaculada Gónzález, Ángela García de la Torre, Maximiliano Ruiz-Galdón","doi":"10.1111/sji.13421","DOIUrl":"10.1111/sji.13421","url":null,"abstract":"<p><p>Multiple sclerosis (MS) diagnosis includes the presence of restricted oligoclonal bands (OCB) in cerebrospinal fluid (CSF), but it has several limitations, as it is an observer-dependent time-consuming technique and offers a dichotomous result. Thus kappa free light chains (KFLC) have emerged as a quantitative alternative. However, the cut-off values for KFLC have not been well established yet and it is not clear if differences between sexes exist. We aim to evaluate these and to compare the diagnostic accuracy of KFLC concentrations and their related indexes versus OCB. For that purpose, paired CSF and serum samples were collected and immediately processed for albumin, total protein, immunoglobulins and OCB, then frozen at -20°C. KFLC was measured in a BN II (Siemens Healthineers, Germany). KFLC-derived indexes were calculated. Diagnostic accuracy was evaluated by the area under the curve (AUC), Youden's index and odds ratio. From the 193 patients included, 56 were classified as MS according to the 2017 McDonald criteria. K-index, Q KFLC and Reiber's diagram showed good accuracy in MS diagnosis when studied distinguishing between sexes, similar to OCB. Cut-offs for K-index and Q KFLC change substantially between sex having the highest AUC similar than OCB. A sex-dependent algorithm combining the use of K-index, Q KFLC and OCB yields the highest diagnostic accuracy. In conclusion, CSF KFLC measurement is a rapid, quantitative and easy-to-standardize tool that used through the proposed sex-dependent algorithm may reduce the number of manual OCB tests performed.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13421"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590959","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}
Mario Sestan, Todor Arsov, Nastasia Kifer, Marijan Frkovic, Danica Grguric, Julia Ellyard, Matthew Cook, Carola G Vinuesa, Marija Jelusic
{"title":"Whole exome sequencing in patients with childhood-onset systemic lupus erythematosus: Results from a Croatian national study.","authors":"Mario Sestan, Todor Arsov, Nastasia Kifer, Marijan Frkovic, Danica Grguric, Julia Ellyard, Matthew Cook, Carola G Vinuesa, Marija Jelusic","doi":"10.1111/sji.13411","DOIUrl":"10.1111/sji.13411","url":null,"abstract":"<p><p>The purpose of this study was to identify new and low-frequency gene variants using whole exome sequencing (WES) in patients with childhood-onset systemic lupus erythematosus (cSLE), that may be involved in the pathogenesis of SLE. We performed WES on selected 17 trios (in some cases including other informative family members) in which the proband presented with severe, atypical clinical features, resistance to conventional therapy, a family pattern of occurrence and/or syndromic characteristics. After performing WES and analysis of gene variants, 17 novel and/or low-frequency variants were identified in 7 patients. One variant was classified as pathogenic (KMT2D, NM_003482.3:c.8626delC, predicted to truncate the protein p.(Gln2876Serfs*34)) and two as likely pathogenic according to the American College of Medical Genetics and Genomics classification guidelines (ADAR, NM_001111.3:c.2815A>G, predicted to encode p.(Ile939Val); BLK, NM_001715.2:c.211G>A, predicted to encode p.(Ala71Thr)). The other variants remain of uncertain significance at this point of time. WES is an important diagnostic and research instrument, producing a growing list of likely genes and gene variants that may be of relevance in the pathogenesis of cSLE and potentially point to novel therapeutic targets.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13411"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392981","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":"F-Box and WD repeat domain containing 7 induces infectious osteomyelitis by regulating MYB stability and ubiquitination.","authors":"Yongbo Wan, Gehan Jiang, Haojie Shan, Yiwei Lin, Wenyang Xia, Fuli Yin, Chaolai Jiang, Zhongmin Shi","doi":"10.1111/sji.13414","DOIUrl":"10.1111/sji.13414","url":null,"abstract":"<p><p>Osteomyelitis is a bone inflammation initiated by invading pathogens. Macrophages and inflammation play essential roles in osteomyelitis. F-Box and WD repeat domain containing 7 (Fbxw7) is a tumour suppressor and E3 ubiquitin ligase. In the present study, the potential roles of Fbxw7 in osteomyelitis were explored. The mRNA level of Fbxw7 was measured in bone marrow cells from patients with osteomyelitis and Staphylococcus aureus (S. aureus)-infected macrophages. The conditional knockout mice with Fbxw7 deficiency in myeloid cells were generated. The expression of interleukin (IL)-6, IL-23a and nitric oxide synthase 2 (Nos2) was measured in S. aureus-infected Fbxw7-deficient bone marrow-derived macrophages (BMDMs). The body weight loss, bacterial burden, bone loss and formation and serum level of IL-6, IL-23 and TNF-α were measured in S. aureus-infected Fbxw7 conditional KO mice. The interacting partners of Fbxw7 were predicted using STRING and the interaction were tested. Elevated expression of Fbxw7 was observed in bone marrow cells from patients with osteomyelitis and in S. aureus-infected macrophages. The expression of IL-6, IL-23a and Nos2 was remarkably suppressed in S. aureus-infected Fbxw7-deficient BMDMs. Fbxw7 conditional knockout mice had less body weight loss, higher bacterial burden, less bone loss and formation and decreased serum level of cytokines. Fbxw7 interacted with MYB. S. aureus-infected Fbxw7-deficient BMDMs had higher level of MYB and less ubiquitination of MYB. Fbxw7 promotes osteomyelitis symptoms by regulating ubiquitination and stability of MYB.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13414"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564876","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}
Sevgi Bilgic-Eltan, Razin Amirov, Royale Babayeva, Melek Yorgun Altunbas, Tuba Karakurt, Salim Can, Ezgi Yalcin Gungoren, Selcen Bozkurt, Necmiye Ozturk, Mehmet Cihangir Catak, Alper Bulutoglu, Gizem Onder, Yuk Yin Ng, Ozden Hatırnaz Ng, Elif Karakoc-Aydiner, Ahmet Oguzhan Ozen, Safa Baris
{"title":"Long-term immunological changes after corrective cardiac surgery.","authors":"Sevgi Bilgic-Eltan, Razin Amirov, Royale Babayeva, Melek Yorgun Altunbas, Tuba Karakurt, Salim Can, Ezgi Yalcin Gungoren, Selcen Bozkurt, Necmiye Ozturk, Mehmet Cihangir Catak, Alper Bulutoglu, Gizem Onder, Yuk Yin Ng, Ozden Hatırnaz Ng, Elif Karakoc-Aydiner, Ahmet Oguzhan Ozen, Safa Baris","doi":"10.1111/sji.13418","DOIUrl":"10.1111/sji.13418","url":null,"abstract":"<p><p>Infants with congenital heart disease (CHD) often undergo thymectomy during corrective cardiac surgery (CCS). The long-term immunological effects remain controversial, with concerns regarding increased susceptibility to infections, allergies, autoimmunity due to compromised immune tolerance mechanisms. This study aims to elucidate the long-term immunological effects of early thymectomy. We enrolled 22 patients who underwent thymectomy in infancy and were followed up in the Pediatric Allergy and Immunology Clinic at Marmara University. We performed demographic characteristics and detailed immunological evaluation, including immunoglobulins, vaccine responses, lymphocyte subset analyses, upregulation, proliferation of T cells and T-cell receptor excision circles (TRECs). Sixteen patients had a history of infection, including six serious infections, all in the first year. Lymphopenia was observed in 27% of patients, with a significant decrease in naive CD4<sup>+</sup> and recent thymic emigrant T cells counts and an increase in the proportion of memory T-cells, indicating premature immune senescence. Low levels of IgG, IgA and IgM were found in 36%, 40% and 22% of patients respectively. Vaccine responses were positive in 90% of patients. TREC levels were low in all 10 patients analysed. Seven of nine patients had normal proliferation. Twenty-two percent of patients had allergic disease, and autoimmunity was not observed. Early thymectomy leads to permanent immunological changes that are indicative of early immunosenescence. It is recommended to preserve thymic tissue during surgery and requires long-term follow-up in terms of findings such as allergy and autoimmunity as well as infections due to impaired immune tolerance mechanisms.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13418"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547140","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}