{"title":"Factors related to seroconversion of anti-cyclic citrullinated peptide antibody after the onset of rheumatoid arthritis: a case-control study and systematic review.","authors":"Yui Kosumi, Ryoko Asano, Aki Sugano, Masaru Yoshimura, Ryo Hisada, Michihito Kono, Yuichiro Fujieda, Tatsuya Atsumi, Masaru Kato","doi":"10.1080/25785826.2025.2565020","DOIUrl":"https://doi.org/10.1080/25785826.2025.2565020","url":null,"abstract":"<p><p>Anti-cyclic citrullinated peptide (CCP) antibodies typically present before rheumatoid arthritis (RA) but appear (seroconvert) after disease onset in some patients. This study analyzed factors related to anti-CCP seroconversion. Fifty-six consecutive patients with anti-CCP negative RA were enrolled. The first determination of anti-CCP status was defined as the baseline. Anti-CCP was then reassessed with an interval of 77 (±41) months. Demographics and baseline characteristics were compared between patients with and without anti-CCP seroconversion. Moreover, relevant studies were systematically reviewed. Six of the 56 patients experienced anti-CCP seroconversion (<4.5-12.4 [8.5-65.7] U/mL). These patients were more likely to have interstitial lung disease and HLA-DRB1 shared epitope (SE) alleles and to use biological disease-modifying antirheumatic drugs (bDMARDs). From the systematic review and meta-analysis, bDMARDs, bone erosions, HLA-DRB1 SE and rheumatoid factor positivity were identified as factors related to anti-CCP seroconversion. By selectively screening for anti-citrullinated protein antibody responses, an expansion of the repertoire was observed after the onset of RA. The seroconversion of anti-CCP after the onset of RA is associated with the typical features of RA and may therefore represent an overlooked seropositive disease.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276064","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 improvement of salt-and-pepper skin changes in juvenile systemic sclerosis using mycophenolate mofetil after intravenous methylprednisolone: a 3-year follow-up.","authors":"Daisuke Hironaka, Hiroyuki Wakiguchi, Fumiko Okazaki, Yuno Korenaga, Yoshihiro Azuma, Akira Tanaka, Reiji Hirano, Yutaka Shimomura, Shunji Hasegawa","doi":"10.1080/25785826.2025.2570899","DOIUrl":"https://doi.org/10.1080/25785826.2025.2570899","url":null,"abstract":"<p><p>In adult systemic sclerosis (SSc), salt-and-pepper skin changes can be used to diagnose diffuse cutaneous SSc during the early stages. However, reports of juvenile SSc (JSSc) with salt-and-pepper skin changes are unavailable. A 12-year-old Japanese girl presented with JSSc, showing scleroderma, Raynaud's phenomenon, digital ulcers, and telangiectasia. She developed scleroderma at 10 years of age and later experienced salt-and-pepper skin changes. Laboratory findings revealed positive antinuclear and anti-U3-RNP antibodies. After being diagnosed with JSSc based on established criteria, she received two courses of intravenous methylprednisolone (IVMP) followed by mycophenolate mofetil (MMF). Her modified Rodnan skin score improved from 25 to 0, and the salt-and-pepper changes resolved. This case represents the first report of the presence and subsequent improvement of salt-and-pepper skin changes in JSSc treated with MMF following IVMP. Recognition of salt-and-pepper changes may serve as an early clinical clue, prompting further diagnostic evaluation for JSSc and supporting early diagnosis of adult SSc. Moreover, MMF after IVMP may exert beneficial anti-fibrotic effects, potentially improving pigment changes by controlling scleroderma.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-5"},"PeriodicalIF":2.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245364","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":"Effect of organism aging on the development of anti-PD-(L)1 therapy-associated adverse events.","authors":"Hirotake Tsukamoto, Kosaku Murakami, Yuji Miura, Yoshihiro Komohara","doi":"10.1080/25785826.2025.2564474","DOIUrl":"https://doi.org/10.1080/25785826.2025.2564474","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI)-mediated release of immune suppression involves the risk of (re)activating the immune responses to self-tissues, which are considered 'side effects' of this therapy, immune-related adverse events (irAEs). Although the incidence of certain types of irAEs appears to be considerably increased in older patients, the effect of chronological aging on irAE development and their causative immunological mechanism are unclear. This review summarizes the potential relevance of chronological and cellular aging, such as age-associated changes in T-cell functions and aged environmental factors, and inflamm-aging, in shaping irAE-inducing immune responses. Several immunological perspectives on aging may provide insights into the practical consideration of the toxicity risks of ICIs, particularly in elderly patients. These insights from patient specimens and pre-clinical animal models will help establishing mechanism-based management strategies, including stratification of irAE-prone patients, and broadening the patient population that benefits from cancer immunotherapy, even in a younger population.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201737","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":"A new era in atopic dermatitis treatment and evolving therapeutic strategies.","authors":"Tetsuya Honda","doi":"10.1080/25785826.2025.2567133","DOIUrl":"https://doi.org/10.1080/25785826.2025.2567133","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a common chronic inflammatory skin disorder whose pathophysiology remained poorly understood until recently. For decades, treatment relied primarily on topical corticosteroids, with no therapies specifically targeting its underlying mechanisms. However, the introduction of dupilumab in 2017 - the first biologic for AD - marked a turning point, catalyzing rapid advances in both therapeutic strategies and pathophysiological insights. As of 2025, four biologics and three oral Janus kinase inhibitors have been approved for clinical use. Additionally, novel topical therapies with distinct mechanisms of action have emerged. Although certain challenges still remain with the use of these novel treatments, AD is increasingly becoming a condition that can be effectively controlled in a wide range of patients.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-13"},"PeriodicalIF":2.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193363","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":"Mechanisms of T cell-mediated immune evasion in cervical cancer: a comprehensive bibliometric analysis and future research directions.","authors":"Xue Bai, Hongxia Wang, Qianyu Guo","doi":"10.1080/25785826.2025.2560214","DOIUrl":"https://doi.org/10.1080/25785826.2025.2560214","url":null,"abstract":"<p><p>Cervical cancer, a prevalent malignancy caused by high-risk HPV strains, remains a significant challenge due to its ability to evade the immune system, particularly T cell-mediated responses. This study aims to explore the research landscape surrounding T cell-mediated immune evasion in cervical cancer through a comprehensive bibliometric analysis. Using data from the Web of Science Core Collection (2014-2023), we employed VOSviewer, CiteSpace, and the R package \"bibliometrics\" to conduct co-citation and co-occurrence analyses, identifying key trends, contributors, and research hotspots. Our analysis included 930 studies from 68 countries, with China, the USA, and the Netherlands as the leading contributors. Emerging topics include immune checkpoint inhibitors, PD-L1, and tumor microenvironment modulation, highlighting the growing focus on immune-based therapies. This study provides valuable insights into the role of T cells in cervical cancer progression and offers a foundation for future research directions aimed at improving immunotherapy outcomes in cervical cancer patients.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-21"},"PeriodicalIF":2.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087626","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":"Life-threatening refractory leukopenia in a patient with systemic lupus erythematosus successfully treated with rituximab.","authors":"Shunichiro Hanai, Yoshiaki Kobayashi, Daiki Nakagomi","doi":"10.1080/25785826.2025.2563427","DOIUrl":"https://doi.org/10.1080/25785826.2025.2563427","url":null,"abstract":"<p><p>Leukopenia can occur because of lymphopenia, neutropenia or both. Leukopenia appearing as a common hematological manifestation of systemic lupus erythematosus (SLE) is typically mild, but potentially life-threatening. However, no consensus has been reached on treatment strategies for severe leukopenia in SLE. An 18-year-old man was diagnosed with SLE based on fever, malar and discoid rash, leukopenia, hypocomplementemia, and a positive result for anti-nuclear antibodies. Despite administration of high-dose glucocorticoids combined with immunosuppressants (including intravenous cyclophosphamide, mycophenolate mofetil, tacrolimus, and azathioprine) and intravenous immunoglobulin G (IgG) treatment, leukocyte count declined to 50/μL, accompanied by positive anti-neutrophil IgG antibodies. Bone marrow biopsy revealed normocellular marrow without hemophagocytosis. The patient developed febrile dyspnea due to pulmonary infection. Administration of rituximab (375 mg/m<sup>2</sup> weekly for 4 weeks) led to rapid, sustained recovery of leukocyte count. The patient then recovered from respiratory failure with anti-microbial therapy. Prednisolone was successfully tapered to 5 mg/day. This case suggests that rituximab may provide an effective therapeutic option for severe treatment-refractory leukopenia in SLE.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-5"},"PeriodicalIF":2.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081918","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":"Macrophage activation syndrome associated with multi-system inflammatory syndrome in children: a case report and cytokine profile.","authors":"Yuji Fujita, Masaki Shimizu, Sayaka Aihara, Kohei Nomura, Shinya Yoshihara, Kaori Sekine, Maho Hatano, Shuya Kaneko, Hideaki Shiraishi","doi":"10.1080/25785826.2025.2559458","DOIUrl":"https://doi.org/10.1080/25785826.2025.2559458","url":null,"abstract":"<p><p>Macrophage activation syndrome (MAS) is a potentially life-threatening complication requiring early diagnosis and prompt treatment in rheumatic diseases such as systemic juvenile idiopathic arthritis (sJIA). Recently, multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was reported to be complicated by MAS. The diagnostic criteria for MAS-associated MIS-C (MIS-C/MAS) remain unknown. We report the case of a 12-year-old boy who presented with fever for 4 days, swollen cervical lymph nodes, conjunctival congestion, red lips, strawberry tongue, irregular erythematous lesions, abdominal pain, and diarrhoea; he had coronavirus disease 2019 (COVID-19) 1 month prior. The patient was diagnosed MIS-C/MAS based on the criteria for sJIA/MAS, treated with intravenous immunoglobulin, glucocorticoids, and cyclosporine without any coronary artery sequelae. Evaluation of the patient's serum cytokine profile revealed that CXCL9 level (14259 pg/mL, reference range <31-83 pg/mL) was significantly elevated, as in sJIA/MAS. Based on cytokine profiles, the diagnostic criteria for MIC-S/MAS may be consistent with those for sJIA/MAS. No previous studies have reported on the cytokine profiles of MIS-C/MAS. Pediatricians should consider that MIS-C may complicate MAS, such as sJIA. Glucocorticoids and cyclosporine may be considered in cases of MIS-C complicated by MAS.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-5"},"PeriodicalIF":2.9,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055876","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":"Comparison of drug retention rates between TNF inhibitors and tocilizumab for Takayasu arteritis: a multicenter retrospective study.","authors":"Takahiro Sugiyama, Shunsuke Furuta, Taro Iwamoto, Kei Ikeda, Shin-Ichiro Kagami, Yasuhiko Kita, Kazuhiro Kurasawa, Shigekazu Takahashi, Daiki Nakagomi, Masaki Hiraguri, Hiroshi Nakajima","doi":"10.1080/25785826.2025.2557038","DOIUrl":"https://doi.org/10.1080/25785826.2025.2557038","url":null,"abstract":"<p><strong>Objective: </strong>We compared the drug retention rate of tumor necrosis factor (TNF) inhibitors (TNFi) and tocilizumab in Takayasu arteritis (TAK) as an index of balance between effectiveness and safety in a real-world setting.</p><p><strong>Method: </strong>We included 50 TAK patients who received biologics in nine hospitals. All patients fulfilled the 1990 American College of Rheumatology classification criteria for TAK. We retrospectively collected clinical information. We analyzed the drug retention rates and the reasons for discontinuation regarding TNFi and tocilizumab.</p><p><strong>Results: </strong>The prednisolone dose at the start of the first biologics was a median of 15 mg/day, and an immunosuppressant was used in 25 patients. Tocilizumab was the most frequent first biologics (64%). Twenty-seven of 32 patients continued on tocilizumab, and four of 18 patients continued on TNFi. The retention rate was significantly higher in tocilizumab than in TNFi (87.9% <i>vs.</i> 66.7% at one year, <i>p</i> = 0.024). The reasons for discontinuing tocilizumab were primary failure in two patients, and other reasons in three. The reasons for discontinuing TNFi were secondary failure in five patients, primary failure in four patients, and other reasons in five.</p><p><strong>Conclusion: </strong>Tocilizumab has a higher continuation rate than TNFi, suggesting that tocilizumab may have better benefit-risk balance for TAK patients.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034364","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 profile of IgG4-related disease in Japan based on the rare disease data registry.","authors":"Motohisa Yamamoto, Masatoshi Kanda, Ichiro Mizushima, Atsushi Kanno, Takeji Umemura, Tsukasa Ikeura, Yuzo Kodama, Hiroaki Dobashi, Yoshiya Tanaka, Atsushi Masamune, Masafumi Moriyama, Takako Saeki, Shoko Matsui, Tomoki Origuchi, Yasufumi Masaki, Masanori Asada, Hisanori Umehara, Hiroshi Seno, Itaru Naitoh, Satoshi Yamamoto, Eisuke Iwasaki, Kensuke Kubota, Shiroh Tanoue, Takayoshi Nishino, Hiroto Tsuboi, Yasushi Matsumoto, Hiroyuki Isayama, Hiroshi Goto, Kenji Notohara, Kazushige Uchida, Ken Kawabe, Kazunori Yamada, Satomi Kasashima, Masayuki Takahira, Yasuharu Sato, Izumi Kawachi, Izumi Yamaguchi, Kazuichi Okazaki, Seiji Nakamura, Fumihiko Matsuda, Hideki Ishikawa, Mitsuhiro Kawano","doi":"10.1080/25785826.2024.2430812","DOIUrl":"10.1080/25785826.2024.2430812","url":null,"abstract":"<p><p>We started a registry for cases of immunoglobulin (Ig)G4-related disease (IgG4-RD) in December 2019 to clarify the clinical profile of IgG4-RD. In this study, clinical information from 854 cases registered by February 16, 2024 was analyzed from multiple perspectives. Diagnosis of IgG4-RD was made in 808 cases, comprising 638 definite, 38 probable, and 132 possible. The mean ± SD age at time of enrollment of the 808 cases was 67.9 ± 11.3 years, with 68.8% being male. The pancreas was the most frequently affected organ (49.8%), followed by the submandibular glands (46.2%) and lacrimal glands (30.6%). This study reconfirmed the pancreas and head-and-neck region as major affected areas in IgG4-RD. Clinically, submandibular adenitis and autoimmune pancreatitis often occur together in the same patient, but no association between the two organs was observed in our analysis. Regarding diagnosis, the comprehensive diagnostic criteria were most commonly used (63.6%). Storiform fibrosis and phlebitis obliterans were detected at different frequencies in different organs. In summary, this registry study identified clinical, imaging, hematologic, and pathologic findings in 808 Japanese patients with IgG4-RD. The frequency of affected organs and their characteristic pathological findings will be particularly useful for future practice.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"192-202"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740875","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":"Expansion of granulocyte-macrophage colony-stimulating factor producing CD4+ T cells in an animal model with enhanced interleukin-1 signal.","authors":"Sho Ishigaki, Keiko Yoshimoto, Mitsuhiro Akiyama, Kotaro Matsumoto, Katsuya Suzuki, Kazuhiro Yamanoi, Yoichiro Iwakura, Tsutomu Takeuchi, Yuko Kaneko","doi":"10.1080/25785826.2024.2430913","DOIUrl":"10.1080/25785826.2024.2430913","url":null,"abstract":"<p><p>Interleukin-1, a pro-inflammatory cytokine, plays a crucial role in inflammatory disease pathogenesis. Interleukin-1 receptor antagonist knockout (IL-1Ra KO) mice spontaneously develop aortitis, arthritis and dermatitis, and are employed as a model for human inflammatory diseases. Previous studies have shown that transferring total T cells from IL-1Ra KO mice into nude mice induces aortitis and arthritis; however, the roles of specific T cell subsets in these inflammatory responses remain unclear. In this study, we aimed to investigate the T cell subsets in IL-1Ra KO mice. We found that the proportion of PD-1+CD44+CD62L-CD4+ T cells in the spleen and lymph nodes of IL-1Ra KO mice was significantly higher than that of wild type mice. RNA sequencing revealed elevated expression of basic helix-loop-helix family member e40 and granulocyte macrophage colony stimulating factor (GM-CSF) in splenic CD44+CD62L-CD4+ T cells from IL-1Ra KO mice. In addition, GM-CSF production from splenic CD4+ T cells of IL-1Ra KO mice was significantly higher than that of wild type mice when stimulated with PMA and ionomycin <i>in vitro</i>. Notably, immunohistochemical staining showed infiltration of GM-CSF+CD4+ T cells at inflammatory sites in IL-1Ra KO mice. Our results suggest that a subset of GM-CSF+CD4 + T cells emerges under IL-1 signal-enhanced inflammatory conditions.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"183-191"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733315","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}