{"title":"Activation of bystander CD8<sup>+</sup> T cells in a pediatric patient with acute hepatitis E.","authors":"Atsushi Morita, Kazuo Imagawa, Tomoya Iwasaki, Katsuyuki Yaita, Aiko Sakai, Hidetoshi Takada","doi":"10.1080/25785826.2024.2378542","DOIUrl":"10.1080/25785826.2024.2378542","url":null,"abstract":"<p><p>Most children with acute hepatitis A virus (HAV) or hepatitis E virus (HEV) infection are asymptomatic. Bystander CD8<sup>+</sup> T-cell activation has garnered attention owing to its possible pathophysiological role in adult hepatitis. However, no reports have studied it in pediatric hepatitis. Herein, we describe the case of a three-year-old girl with acute hepatitis by HEV genotype 1. She had a history of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, and HEV hepatitis occurred shortly after asymptomatic HAV infection. Peripheral immunophenotyping revealed activation of non-HEV-specific CD8<sup>+</sup> T cells which include EBV-specific and CMV-specific CD8<sup>+</sup> T cells, during the acute phase. While alanine-aminotransferase levels declined after admission, the total number of activated CD8<sup>+</sup> T cells increased for four days after admission and decreased thereafter. In contrast, activation of EBV-specific and CMV-specific CD8<sup>+</sup> T cells was almost at the maximal level at the time of admission, which suggest development of activated bystander CD8<sup>+</sup> T cells in the early stage. This case highlights the significance of the bystander CD8<sup>+</sup> T-cell activation even in pediatric hepatitis and the size of the CD8<sup>+</sup> T cell memory pool in the individuals for the development of hepatitis, given the patient's history of infections with EBV, CMV and HAV.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"278-284"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627982","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}
Immunological MedicinePub Date : 2024-12-01Epub Date: 2024-06-28DOI: 10.1080/25785826.2024.2372869
Keisuke Maeshima
{"title":"Herpes zoster in the context of immune reconstitution inflammatory syndrome in patients with rheumatic diseases: a single-center retrospective study.","authors":"Keisuke Maeshima","doi":"10.1080/25785826.2024.2372869","DOIUrl":"10.1080/25785826.2024.2372869","url":null,"abstract":"<p><p>Immune reconstitution inflammatory syndrome (IRIS) experienced in rheumatology practice is diverse and includes opportunistic infections such as herpes zoster (HZ). This study aimed to explore the risk of HZ in patients with rheumatic diseases in the perspective of IRIS. The study retrospectively reviewed the clinical courses of 20 patients with HZ and investigated the IRIS triggers such as the reduction or discontinuation of immunosuppressive drugs within 3 months and coronavirus disease 2019 (COVID-19) vaccination within 4 weeks prior to HZ development. Disease activity of the underlying rheumatic disease at HZ onset was evaluated using the physician's global assessment. Thirteen patients developed HZ after reducing or discontinuing immunosuppressive drugs, with mild and stable disease activity. In four of these cases, disease activity increased after dose reduction or discontinuation, and HZ subsequently developed. Two of the seven patients who did not reduce or discontinue immunosuppressive drugs received the COVID-19 vaccination. Fifteen patients (75%) had at least one of the two IRIS triggers. Four of the five patients who developed HZ without any IRIS triggers were at HZ risk. To conclude, IRIS, caused by the reduction or discontinuation of immunosuppressive drugs, may be involved in the development of HZ in rheumatology practice.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"247-253"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471303","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":"Clinical features of flare in Japanese patients with new-onset SLE and risk factors for SLE flare in daily clinical practice: a single-center cohort study.","authors":"Shuzo Sato, Shuhei Yoshida, Yuya Sumichika, Kenji Saito, Haruki Matsumoto, Jumpei Temmoku, Yuya Fujita, Naoki Matsuoka, Tomoyuki Asano, Kiyoshi Migita","doi":"10.1080/25785826.2024.2360664","DOIUrl":"10.1080/25785826.2024.2360664","url":null,"abstract":"<p><p>This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan-Meier's curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan-Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"230-237"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200528","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":"Comparative analysis of renal decline rates in microscopic polyangiitis: unveiling the slowly progressive phenotype.","authors":"Kanako Tsutsumi, Narumichi Iwamura, Katsumi Eguchi, Ayuko Takatani, Tomohiro Koga, Takeshi Araki, Toshiyuki Aramaki, Kaoru Terada, Yukitaka Ueki","doi":"10.1080/25785826.2024.2366313","DOIUrl":"10.1080/25785826.2024.2366313","url":null,"abstract":"<p><p>Although rapidly progressive glomerulonephritis (RPGN) is the main renal phenotype of microscopic polyangiitis (MPA), we aim to clarify the clinical features of slowly progressive MPA. This retrospective observational study included 12 patients diagnosed with MPA in our hospital between January 2012 and February 2022. We investigated the differences in surrogate markers, rate of decline of estimated glomerular filtration rate (eGFR) between the slowly progressive and rapidly progressive MPA groups. Of the 12 patients with MPA, 3 (25.0%) had slowly progressive MPA: MPA within 30% decrease in eGFR 3 months pretreatment, all of whom developed RPGN during the course. Patients with slowly progressive MPA had lower levels of C-reactive protein, myeloperoxidase anti-neutrophil cytoplasmic antibodies, and interleukin-6; higher levels of sialylated carbohydrate antigen KL-6. Slowly progressive MPA is not uncommon in our hospital. A linear relationship was found between slower rate of eGFR decline and lower surrogate markers of disease activity. Some MPA cases have slowly progressive glomerulonephritis leading to RPGN, which may be clinically characterized by low disease activity. It may be useful to measure myeloperoxidase anti-neutrophil cytoplasmic antibody in chronic kidney disease with concomitant urinary abnormalities to diagnose MPA with slowly progressive glomerulonephritis.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"254-263"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440939","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":"Anti-aminoacyl tRNA synthetase antibodies showing the discrepancy between enzyme-linked immunosorbent assay and RNA-immunoprecipitation.","authors":"Tsuneo Sasai, Yuki Ishikawa, Ran Nakashima, Takuya Isayama, Kiminobu Tanizawa, Tomohiro Handa, Mirei Shirakashi, Ryosuke Hiwa, Hideaki Tsuji, Koji Kitagori, Shuji Akizuki, Hajime Yoshifuji, Tsuneyo Mimori, Akio Morinobu","doi":"10.1080/25785826.2024.2328918","DOIUrl":"10.1080/25785826.2024.2328918","url":null,"abstract":"<p><p>Anti-aminoacyl-tRNA synthetase (ARS) antibodies are myositis-specific antibodies associated with anti-synthetase syndrome (ASSD). Some patients are positive for anti-ARS antibodies on enzyme-linked immunosorbent assay (ELISA) but negative on RNA-immunoprecipitation (RNA-IP) (the gold standard method). Whether these patients should be considered truly positive for anti-ARS antibodies remains unclear. Therefore, we investigated the clinical characteristics of these patients and verified the authenticity of their anti-ARS positivity. Patients who were positive for anti-ARS antibodies on ELISA were divided into the non-discrepant (positive on RNA-IP, <i>n</i> = 52) and discrepant (negative on RNA-IP, <i>n</i> = 8) groups. Patient clinical characteristics were compared between the groups. For each positive individual, the authenticity of anti-ARS antibody positivity on ELISA was cross-examined using protein-IP and western blotting. All patients in the discrepant group had lung involvement, including five (63%) with interstitial lung disease. The overall survival time was significantly lower in the discrepant group than in the non-discrepant group (<i>p</i> < 0.05). Validation tests confirmed the presence of anti-ARS antibodies in the sera of the discrepant group but indicated different reactivity from typical anti-ARS antibodies. In conclusion, some anti-ARS antibodies are detected by ELISA but not RNA-IP. Such anti-ARS antibody discrepancies need further elucidation to attain validation of the diagnostic process in ASSD.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"166-175"},"PeriodicalIF":2.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132804","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":"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":" ","pages":"186-191"},"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":" ","pages":"151-165"},"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<sup>+</sup> NB cells, whose numbers are increased in NMOSD patients, have a greater capacity to differentiate into ASCs than do CD25<sup>-</sup> 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<sup>+</sup> NB, CD25<sup>-</sup> 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<sup>+</sup> NB-LCLs derived from patients with NMOSD exhibited a greater capacity to differentiate into SMB-LCLs than did CD25<sup>-</sup> 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":" ","pages":"142-150"},"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":" ","pages":"176-185"},"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":" ","pages":"118-129"},"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}