Immunological Medicine最新文献

{"title":"Impact of multiple <i>MEFV</i> variants of unknown significance on the diagnosis and clinical presentation of familial Mediterranean fever.","authors":"Dai Kishida, Masahide Yazaki, Akinori Nakamura, Ayako Tsuchiya-Suzuki, Takanori Ichikawa, Yasuhiro Shimojima, Yoshiki Sekijima","doi":"10.1080/25785826.2024.2358587","DOIUrl":"10.1080/25785826.2024.2358587","url":null,"abstract":"<p><p>The detection of variants of unknown significance (VUS) in familial Mediterranean fever (FMF) is common; however, their diagnostic value remains elusive, and the interpretation of multiple VUS remains difficult. Therefore, we examined FMF diagnosis-associated factors 1-year post-genetic testing in patients with only VUS and assessed the impact of multiple VUS on diagnosis and clinical features. A 1-year follow-up was conducted on patients clinically suspected of having FMF without confirmatory diagnosis owing to the presence of only VUS. Clinical features were compared between patients with a single VUS and those with multiple VUS among patients diagnosed with FMF. Among 261 patients followed up, 202 were diagnosed with FMF based on clinical judgment. No specific clinical symptoms or variant patterns at genetic testing were associated with diagnosis at 1 year. Multiple VUS was significantly and independently associated with a lower response to colchicine than single VUS among patients diagnosed with FMF. However, clinical symptoms showed no correlation with the number of VUS. In conclusion, predicting FMF diagnosis 1-year post-genetic testing in patients with only VUS remains challenging. Moreover, the impact of multiple VUS on FMF may be limited owing to the lack of correlation with clinical features, except colchicine response.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High frequency of circulating non-classical monocytes is associated with stable remission in relapsing-remitting multiple sclerosis.","authors":"Misako Minote, Wakiro Sato, Kimitoshi Kimura, Atsuko Kimura, Youwei Lin, Tomoko Okamoto, Ryosuke Takahashi, Takashi Yamamura","doi":"10.1080/25785826.2024.2331271","DOIUrl":"10.1080/25785826.2024.2331271","url":null,"abstract":"<p><p>'No evidence of disease activity (NEDA)', judged by clinical and radiological findings, is a therapeutic goal in patients with multiple sclerosis (MS). It is, however, unclear if distinct biological mechanisms contribute to the maintenance of NEDA. To clarify the immunological background of long-term disease stability defined by NEDA, circulating immune cell subsets in patients with relapsing-remitting MS (RRMS) were analyzed using flow cytometry. Patients showing long-term NEDA (<i>n</i> = 31) had significantly higher frequencies of non-classical monocytes (NCMs) (6.1% vs 1.4%) and activated regulatory T cells (Tregs; 2.1% vs 1.6%) than those with evidence of disease activity (<i>n</i> = 8). The NCM frequency and NCMs to classical monocytes ratio (NCM/CM) positively correlated with activated Treg frequency and duration of NEDA. Co-culture assays demonstrated that NCMs could increase the frequency of activated Tregs and the expression of PD-L1, contributing to development of Tregs, was particularly high in NCMs from patients with NEDA. Collectively, NCMs contribute to stable remission in patients with RRMS, possibly by increasing activated Treg frequency. In addition, the NCM frequency and NCM/CM ratio had high predictive values for disease stability (AUC = 0.97 and 0.94, respectively), suggesting these markers are potential predictors of a long-term NEDA status in RRMS.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of novel cell lines that maintain the features of B cells derived from patients with neuromyelitis optica spectrum disorder.","authors":"Shuhei Sano, Soichiro Yoshikawa, Yasunobu Hoshino, Yuji Tomizawa, Nobutaka Hattori, Sachiko Miyake","doi":"10.1080/25785826.2024.2334002","DOIUrl":"10.1080/25785826.2024.2334002","url":null,"abstract":"<p><p>B cells that produce anti-aquaporin-4 (AQP4) antibodies play a crucial role in neuromyelitis optica spectrum disorder (NMOSD) pathogenesis. We previously reported that naïve B (NB) cells from patients with NMOSD, unlike those from healthy controls, exhibit transcriptional changes suggesting the adoption of an antibody-secreting cell (ASCs) phenotype. CD25⁺ NB cells, whose numbers are increased in NMOSD patients, have a greater capacity to differentiate into ASCs than do CD25^- NB cells. Here, we attempted to establish novel B cell subset cell lines from patients with NMOSD to enable molecular analysis of their abnormalities. We generated Epstein-Barr virus-immortalized lymphoblastoid cell lines (LCLs) from CD25⁺ NB, CD25^- NB, and switched memory B (SMB) cells. All LCLs largely maintained the features of the original cell type in terms of cell surface marker expression and could differentiate into ASCs. Notably, CD25⁺ NB-LCLs derived from patients with NMOSD exhibited a greater capacity to differentiate into SMB-LCLs than did CD25^- NB-LCLs derived from patients with NMOSD, suggesting that the established LCLs maintained the characteristics of cells isolated from patients. The LCLs established in this study are likely to be useful for elucidating the mechanism by which cells that produce anti-AQP4 antibodies develop in NMOSD.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARID5B is a negative modulator of IL-6 production in rheumatoid arthritis synovial fibroblasts.","authors":"Yasuhiro Tagawa, Tetsuya Saito, Hideyuki Iwai, Motohiko Sato, Seiji Noda, Akio Yamamoto, Mineto Ota, Kentaro Endo, Hideyuki Koga, Yasuhiro Takahara, Kazutaka Sugimoto, Ichiro Sekiya, Keishi Fujio, Eiryo Kawakami, Fumitaka Mizoguchi, Shinsuke Yasuda","doi":"10.1080/25785826.2024.2346956","DOIUrl":"10.1080/25785826.2024.2346956","url":null,"abstract":"<p><p>Recent single-cell RNA-sequencing analysis of rheumatoid arthritis (RA) synovial tissues revealed the heterogeneity of RA synovial fibroblasts (SFs) with distinct functions such as high IL-6 production. The molecular mechanisms responsible for high IL-6 production will become a promising drug target of RASFs to treat RA. In this study, we performed siRNA screening of 65 transcription factors (TFs) differentially expressed among RASF subsets to identify TFs involved in IL-6 production. The siRNA screening identified 7 TFs including <i>ARID5B</i>, a RA risk gene, that affected IL-6 production. Both long and short isoforms of ARID5B were expressed and negatively regulated by TNF-α in RASFs. The siRNA knockdown and lentiviral overexpression of long and short isoforms of ARID5B revealed that the long isoform suppressed IL-6 production stimulated with TNF-α. eQTL analysis using 58 SFs demonstrated that RA risk allele, rs10821944, in intron 4 of the <i>ARID5B</i> gene had a trend of eQTL effects to the expression of long isoform of ARID5B in SFs treated with TNF-α. ARID5B was found to be a negative modulator of IL-6 production in RASFs. The RA risk allele of <i>ARID5B</i> intron may cause high IL-6 production, suggesting that ARID5B will become a promising drug target to treat RA.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single cell analysis in systemic sclerosis - A systematic review.","authors":"Takemichi Fukasawa, Asako Yoshizaki-Ogawa, Atsushi Enomoto, Takashi Yamashita, Kiyoshi Miyagawa, Shinichi Sato, Ayumi Yoshizaki","doi":"10.1080/25785826.2024.2360690","DOIUrl":"10.1080/25785826.2024.2360690","url":null,"abstract":"<p><p>In recent years, rapid advances in research methods have made single cell analysis possible. Systemic sclerosis (SSc), a disease characterized by the triad of immune abnormalities, fibrosis, and vasculopathy, has also been the subject of various analyses. To summarize the results of single cell analysis in SSc accumulated to date and to deepen our understanding of SSc. Four databases were used to perform a database search on 23rd June 2023. Assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed according to PRISMA guidelines. The analysis was completed on July 2023. 17 studies with 358 SSc patients were included. Three studies used PBMCs, six used skin, nine used lung with SSc-interstitial lung diseases (ILDs), and one used lung with SSc-pulmonary arterial hypertension (PAH). The cells studied included immune cells such as T cells, natural killer cells, monocytes, macrophages, and dendritic cells, as well as endothelial cells, fibroblasts, keratinocytes, alveolar type I cells, basal epithelial cells, smooth muscle cells, mesothelial cells, etc. This systematic review revealed the results of single cell analysis, suggesting that PBMCs, skin, SSc-ILD, and SSc-PAH show activation and dysfunction of cells associated with immune-abnormalities, fibrosis, and vasculopathy, respectively.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety risks of interstitial lung disease upon real-world usage of Janus kinase inhibitors and biologics for patients with autoimmune diseases: epidemiological study using nationwide electronic medical record database in Japan.","authors":"Mihoko Yabuuchi, Kazuhito Yokoyama","doi":"10.1080/25785826.2024.2311763","DOIUrl":"10.1080/25785826.2024.2311763","url":null,"abstract":"<p><p>Although Janus kinase inhibitor (JAKi) therapy is used for patients with autoimmune diseases (AD), one safety concern, interstitial lung disease (ILD), is life-threatening. We evaluated actual usage of JAKi and safety upon JAKi treatment, in an epidemiological retrospective cohort study utilizing the electronic medical record database in Japan. Among 391,565 AD patients, we analyzed data of new-users receiving JAKi or tumor necrosis factor alpha inhibitor (TNFi)/biologics during the period July 2013-May 2022. ILD (ICD10: J70.2, J70.3, J70.4 and J84) criteria were defined: new-ILD (1) and new-ILD (2) which differed in the latter's prompter therapeutics cessation upon ILD development. We analyzed ILD occurrence and death, ILD cumulative incidence by the Kaplan-Meier method, and hazard ratio (HR) by the Cox model, for 957 JAKi and 3931 TNFi users. JAKi use has become widespread amidst additional drug-development. Among JAKi users, two-year new-ILD (2) incidence, at 1.4%, was higher than for TNFi users (risk ratio: new-ILD (2) 1.75, death 2.31). Cumulative incidence (2.9% in 20.48 days) was also significantly higher (log-rank test <i>p</i> = .013, HR 2.23 (95% CI 1.16-4.27)); risk factors estimated by HR included JAKi (2.14), rheumatoid arthritis (4.94), diabetes mellitus (2.67) and cerebrovascular disease (2.86). ILD screening is essential.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale cross-trait genetic analysis highlights shared genetic backgrounds of autoimmune diseases.","authors":"Yuji Yamamoto, Yuya Shirai, Ryuya Edahiro, Atsushi Kumanogoh, Yukinori Okada","doi":"10.1080/25785826.2024.2394258","DOIUrl":"https://doi.org/10.1080/25785826.2024.2394258","url":null,"abstract":"<p><p>Disorders associated with the immune system burden multiple organs, although the shared biology exists across the diseases. Preceding family-based studies reveal that immune diseases are heritable to varying degrees, providing the basis for immunogenomics. The recent cost reduction in genetic analysis intensively promotes biobank-scale studies and the development of frameworks for statistical genetics. The accumulating multi-layer omics data, including genome-wide association studies (GWAS) and RNA-sequencing at single-cell resolution, enable us to dissect the genetic backgrounds of immune-related disorders. Although autoimmune and allergic diseases are generally categorized into different disease categories, epidemiological studies reveal the high incidence of autoimmune and allergic disease complications, suggesting the shared genetics and biology between the disease categories. Biobank resources and consortia cover multiple immune-related disorders to accumulate phenome-wide associations of genetic variants and enhance researchers to analyze the shared and heterogeneous genetic backgrounds. The emerging post-GWAS and integrative multi-omics analyses provide genetic and biological insights into the multicategorical disease associations.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in immunological profile in atopic dermatitis patients with and without dupilumab therapy.","authors":"Jarmila Čelakovská, Eva Čermáková, Petra Boudková, Ctirad Andýs, Jan Krejsek","doi":"10.1080/25785826.2024.2387882","DOIUrl":"https://doi.org/10.1080/25785826.2024.2387882","url":null,"abstract":"<p><p>Our aim is to determine the number of leukocytes, T lymphocytes and B lymphocytes and the expression of activation markers CD200 and CD23 on B lymphocytes in atopic dermatitis (AD) patients (treated and not treated with dupilumab) during the pollen season. We examined 29 patients not treated with dupilumab, 24 patients treated with dupilumab and 40 healthy subjects as a control group. The count of T and B lymphocytes and their subsets were assessed by flow cytometry. The non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni's modification was used for statistical processing. Although there was a significant improvement in skin findings in patients treated with dupilumab, the changes in immunological profile show a persistent altered immune response characterized by dysregulation and overactivation of B lymphocytes. Dupilumab therapy leads to normalization of relative T regulatory lymphocytes and total memory B lymphocytes and to decreased count of absolute CD8⁺ T lymphocytes.<b>Why carry out this study?</b>Studies investigating the immunological profile of atopic dermatitis (AD) patients during the pollen season are rare. There are no studies investigating the count of B lymphocytes (CD5⁺, CD22⁺ and CD73⁺ B lymphocytes) and the expression of activation markers CD23 and CD200 on B lymphocytes and on their subsets during pollen season in AD patients treated and non-treated with dupilumab therapy.<b>What was learned from the study?</b>In atopic dermatitis (AD) patients with and without dupilumab therapy, we confirmed the significantly higher count of absolute neutrophils, absolute monocytes, absolute eosinophils, absolute basophils, non-switched B lymphocytes, transitional B lymphocytes, CD23 memory, naive, non-switched, switched and total CD23 B lymphocytes, the relative count of CD200 memory and CD200 switched B lymphocytes.In dupilumab treated patients, we confirmed the significantly higher count of relative eosinophils, relative CD16⁺ eosinophils, relative CD200 non-switched B lymphocytes and lower count of absolute CD8⁺ T lymphocytes. Further studies should focus on investigating the effect of dupilumab on CD8⁺ T lymphocytes and their subpopulations.In patients without dupilumab therapy, we confirmed the significantly higher count of relative neutrophils, relative T regulatory lymphocytes and total memory B lymphocytes.The changes in the count of CD5⁺, CD22⁺ and CD73⁺ B lymphocytes were not observed during pollen season in both groups of AD patients.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling immune cell heterogeneity in autoimmune arthritis: insights from single-cell RNA sequencing.","authors":"Sotaro Nakajima, Haruka Tsuchiya, Keishi Fujio","doi":"10.1080/25785826.2024.2388343","DOIUrl":"https://doi.org/10.1080/25785826.2024.2388343","url":null,"abstract":"<p><p>Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of immune-mediated arthritis, which comprises rheumatoid arthritis and spondyloarthritis. This review outlines the key findings and advancements in scRNA-seq studies focused on the pathogenesis of autoimmune arthritis and its clinical application. In rheumatoid arthritis, scRNA-seq has elucidated the heterogeneity among synovial fibroblasts and immune cell subsets in inflammatory sites, offering insights into disease mechanisms and the differences in treatment responses. Various studies have identified distinct synovial fibroblast subpopulations, such as <i>THY1</i>⁺ inflammatory and <i>THY1</i>^- destructive fibroblasts. Furthermore, scRNA-seq has revealed diverse T cell profiles in the synovium, including peripheral helper T cells and clonally expanded CD8⁺ T cells, shedding light on potential therapeutic targets and predictive markers of treatment response. Similarly, in spondyloarthritis, particularly psoriatic arthritis and ankylosing spondylitis, scRNA-seq studies have identified distinct cellular profiles associated with disease pathology. Challenges such as cost and sample size limitations persist, but collaborative efforts and utilization of public databases hold promise for overcoming these obstacles. Overall, scRNA-seq emerges as a powerful tool for dissecting cellular heterogeneity and driving precision medicine in immune-mediated arthritis.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful maintenance therapy with tocilizumab for severe acute liver failure associated with adult-onset still's disease.","authors":"Koji Suzuki, Mitsuhiro Akiyama, Yukie Nakadai, Shingo Usui, Yuko Kaneko","doi":"10.1080/25785826.2024.2388346","DOIUrl":"https://doi.org/10.1080/25785826.2024.2388346","url":null,"abstract":"<p><p>Elevated liver enzymes are commonly observed among adult-onset Still's disease (AOSD), but severe acute liver failure is extremely rare. Although severe acute liver failure associated with AOSD poses a life-threatening condition, the appropriate treatment is unclear. Some case reports have demonstrated the efficacy of high-dose prednisolone (PSL) and cyclosporin A (CyA), although the adverse effects of CyA led certain patients to cease its use. Therefore, an alternative treatment option is crucial, and thus far, there have been no reports of tocilizumab (TCZ) being used for this severe phenotype. Here, we report the first case of successful treatment using TCZ as maintenance therapy for severe ALF associated with AOSD. Following initial treatment with high-dose PSL and CyA, our case was switched to TCZ due to CyA-related side effects including alopecia and tremors. Our case highlights TCZ as a potential option for maintenance therapy of this severe condition.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}