Immunological Medicine最新文献_第7页

Successful treatment with tofacitinib for anti-melanoma differentiation-associated gene 5 antibody-positive juvenile dermatomyositis: case reports and review of the literature. 用托法替尼成功治疗抗黑素瘤分化相关基因5抗体阳性的幼年皮肌炎：病例报告和文献综述。

IF 4.4

Immunological Medicine Pub Date : 2024-06-01 Epub Date: 2024-04-01 DOI: 10.1080/25785826.2024.2336687

Susumu Yamazaki, Masaki Shimizu, Ayane Yakabe, Eisuke Inage, Keisuke Jimbo, Mitsuyoshi Suzuki, Futaba Miyaoka, Shuya Kaneko, Hitoshi Irabu, Asami Shimbo, Yoshiyuki Ohtomo, Masaaki Mori, Tomohiro Morio, Toshiaki Shimizu

{"title":"Successful treatment with tofacitinib for anti-melanoma differentiation-associated gene 5 antibody-positive juvenile dermatomyositis: case reports and review of the literature.","authors":"Susumu Yamazaki, Masaki Shimizu, Ayane Yakabe, Eisuke Inage, Keisuke Jimbo, Mitsuyoshi Suzuki, Futaba Miyaoka, Shuya Kaneko, Hitoshi Irabu, Asami Shimbo, Yoshiyuki Ohtomo, Masaaki Mori, Tomohiro Morio, Toshiaki Shimizu","doi":"10.1080/25785826.2024.2336687","DOIUrl":"10.1080/25785826.2024.2336687","url":null,"abstract":"Although the clinical efficacy of tofacitinib has been reported in adult patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (Ab+) dermatomyositis, data on its use in refractory juvenile dermatomyositis (JDM) are scarce. We describe two female Japanese patients with anti-MDA5 Ab + JDM and rapidly progressive interstitial lung disease who achieved remission by adding tofacitinib to existing immunosuppressive drugs and present a literature review. While both patients received various immunosuppressive or anti-inflammatory treatments for induction therapy, remission could not be achieved. Subsequently, tofacitinib was administered to reduce the Krebs von den Lungen-6 level 5 months after diagnosis in one patient; the other patient received tofacitinib 4 months after diagnosis to reduce ferritin levels and skin manifestations. Subsequently, both patients achieved remission, and prednisolone was withdrawn. Tofacitinib reduced the interferon signature associated with dermatomyositis/JDM disease progression and exerted a therapeutic effect on dermatomyositis/JDM. We found six published cases from five articles of tofacitinib for refractory anti-MDA5 Ab + JDM. Except for one case of herpes simplex meningitis, the other cases, including ours, had improved disease activity without severe adverse events, and steroids and immunosuppressive medicines could be tapered. Tofacitinib could be considered an available therapy for refractory anti-MDA5 Ab + JDM.","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"110-117"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337096","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}

引用次数: 0

Possible correlation between serum interleukin-8 levels and the activity of myositis in anti-NXP2 antibody-positive dermatomyositis. 抗 NXP2 抗体阳性皮肌炎患者血清白细胞介素-8 水平与肌炎活动之间可能存在的相关性

IF 4.4

Immunological Medicine Pub Date : 2024-06-01 Epub Date: 2024-01-04 DOI: 10.1080/25785826.2023.2300553

Risa Konishi, Yuki Ichimura, Ryota Tanaka, Hanako Miyahara, Mari Okune, Masahide Miyamoto, Monami Hara, Atsushi Iwabuchi, Hidetoshi Takada, Yasuo Nakagishi, Mao Mizuta, Shuya Kaneko, Masaki Shimizu, Tomohiro Morio, Ichizo Nishino, Toshifumi Nomura, Naoko Okiyama

{"title":"Possible correlation between serum interleukin-8 levels and the activity of myositis in anti-NXP2 antibody-positive dermatomyositis.","authors":"Risa Konishi, Yuki Ichimura, Ryota Tanaka, Hanako Miyahara, Mari Okune, Masahide Miyamoto, Monami Hara, Atsushi Iwabuchi, Hidetoshi Takada, Yasuo Nakagishi, Mao Mizuta, Shuya Kaneko, Masaki Shimizu, Tomohiro Morio, Ichizo Nishino, Toshifumi Nomura, Naoko Okiyama","doi":"10.1080/25785826.2023.2300553","DOIUrl":"10.1080/25785826.2023.2300553","url":null,"abstract":"Anti-nuclear matrix protein 2 (NXP2) antibody-positive dermatomyositis (DM) is characterized by extensive and severe myositis. In this study, we evaluated which cytokines/chemokines involved with the activity of the myositis. We performed quantitative immunoassays using the MILLIPLEX® Multiplex Assays Using Luminex to evaluate serum levels of interferon-γ, interleukin (IL)-1β, IL-6, IL-8, IL-12p40, and tumor necrosis factor-α in samples collected over time from a 9-year-old female with anti-NXP2 antibody-positive DM. In our case, the serum level of IL-8 was elevated when the myositis worsened, and decreased in accordance with the improvement of myositis, suggesting that the serum IL-8 levels were correlated with the myositis activity. Serum levels of IL-8 in samples from five patients with anti-NXP2 antibody-positive DM and five patients with anti-transcriptional intermediary factor 1γ (TIF1γ) antibody-positive DM without both interstitial lung disease (ILD) and malignancy before starting treatments, along with five healthy controls, were also evaluate by an enzyme-linked immunosorbent assay. Serum IL-8 levels were significantly elevated in anti-NXP2 or anti-TIF1γ antibody-positive DM patients with myositis but not ILD, than healthy controls. It was suggested that serum levels of IL-8 correlate with the activity of myositis in DM including anti-NXP2 antibody-positive DM.","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"100-105"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088924","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}

引用次数: 0

NF9 peptide specific cytotoxic T lymphocyte clone cross react to Y453F mutation of SARS-CoV-2 virus spike protein. NF9肽特异性细胞毒性T淋巴细胞克隆与SARS-CoV-2病毒尖峰蛋白Y453F突变产生交叉反应。

IF 4.4

Immunological Medicine Pub Date : 2024-06-01 Epub Date: 2024-01-18 DOI: 10.1080/25785826.2024.2304363

Aiko Murai, Terufumi Kubo, Takayuki Ohkuri, Junko Yanagawa, Yuki Yajima, Akemi Kosaka, Dongliang Li, Toshihiro Nagato, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Takeshi Nagasaki, Yoshihiko Hirohashi, Hiroya Kobayashi, Toshihiko Torigoe

{"title":"NF9 peptide specific cytotoxic T lymphocyte clone cross react to Y453F mutation of SARS-CoV-2 virus spike protein.","authors":"Aiko Murai, Terufumi Kubo, Takayuki Ohkuri, Junko Yanagawa, Yuki Yajima, Akemi Kosaka, Dongliang Li, Toshihiro Nagato, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Takeshi Nagasaki, Yoshihiko Hirohashi, Hiroya Kobayashi, Toshihiko Torigoe","doi":"10.1080/25785826.2024.2304363","DOIUrl":"10.1080/25785826.2024.2304363","url":null,"abstract":"The recognition by cytotoxic T cells (CTLs) is essential for the clearance of SARS-CoV-2 virus-infected cells. Several viral proteins have been described to be recognized by CTLs. Among them, the spike (S) protein is one of the immunogenic proteins. The S protein acts as a ligand for its receptors, and several mutants with different affinities for its cognate receptors have been reported, and certain mutations in the S protein, such as L452R and Y453F, have been found to inhibit the HLA-A24-restricted CTL response. In this study, we conducted a screening of candidate peptides derived from the S protein, specifically targeting those carrying the HLA-A24 binding motif. Among these peptides, we discovered that NF9 (NYNYLYRLF) represents an immunogenic epitope. CTL clones specific to the NF9 peptide were successfully established. These CTL clones exhibited the ability to recognize endogenously expressed NF9 peptide. Interestingly, the CTL clone demonstrated cross-reactivity with the Y453F peptide (NYNYLFRLF) but not with the L452R peptide (NYNYRYRLF). The CTL clone was able to identify the endogenously expressed Y453F mutant peptide. These findings imply that the NF9-specific CTL clone possesses the capability to recognize and respond to the Y453F mutant peptide.","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"93-99"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485778","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}

引用次数: 0

Efficacy and safety of mycophenolate mofetil for steroid reduction in neuromyelitis optica spectrum disorder: a prospective cohort study. 前瞻性队列研究：霉酚酸酯减少神经脊髓炎视网膜频谱障碍类固醇用药的有效性和安全性。

IF 2.7

Immunological Medicine Pub Date : 2024-06-01 Epub Date: 2024-01-18 DOI: 10.1080/25785826.2024.2304364

Ritsu Akatani, Norio Chihara, Shusuke Koto, Sotaro Mori, Takuji Kurimoto, Makoto Nakamura, Hisatsugu Tachibana, Yoshihisa Otsuka, Takehiro Ueda, Takashi Omori, Kenji Sekiguchi, Riki Matsumoto

引用次数: 0

Synovial-tissue resident macrophages play proinflammatory functions in the pathogenesis of RA while maintaining the phenotypes in the steady state. 滑膜组织常住巨噬细胞在 RA 的发病机制中发挥促炎功能，同时在稳定状态下保持表型。

IF 4.4

Immunological Medicine Pub Date : 2024-06-01 Epub Date: 2024-01-03 DOI: 10.1080/25785826.2023.2300853

Kazuhiro Kai, Hisakata Yamada, Ryosuke Tsurui, Koji Sakuraba, Kenjiro Fujimura, Shinya Kawahara, Yukio Akasaki, Hidetoshi Tsushima, Toshifumi Fujiwara, Daisuke Hara, Jun-Ichi Fukushi, Shinichiro Sawa, Yasuharu Nakashima

{"title":"Synovial-tissue resident macrophages play proinflammatory functions in the pathogenesis of RA while maintaining the phenotypes in the steady state.","authors":"Kazuhiro Kai, Hisakata Yamada, Ryosuke Tsurui, Koji Sakuraba, Kenjiro Fujimura, Shinya Kawahara, Yukio Akasaki, Hidetoshi Tsushima, Toshifumi Fujiwara, Daisuke Hara, Jun-Ichi Fukushi, Shinichiro Sawa, Yasuharu Nakashima","doi":"10.1080/25785826.2023.2300853","DOIUrl":"10.1080/25785826.2023.2300853","url":null,"abstract":"Synovial tissue-resident macrophages (STRMs) maintain normal joint homeostasis in a steady state. However, it is unclear whether STRMs still play homeostatic roles or change the functions in the joint of rheumatoid arthritis (RA), where infiltrating peripheral blood monocyte-derived macrophages (PBMoMs) play proinflammatory roles. In the present study, we examined changes in the phenotypes and functions of STRMs in response to RA-related stimuli in vitro. STRMs were prepared from non-inflammatory osteoarthritis (OA) joint synovium, which is histologically indistinguishable from normal joint synovium. PBMoMs were prepared and used for comparison. After stimulation with plate-bound IgG, which mimics anti-citrullinated protein antibody immunocomplex formed in RA joints, or with combinations of RA-related inflammatory mediators, namely tumor necrosis factor-α (TNF-α) and prostaglandin E2 or interferon-γ, PBMoMs downregulated surface markers and genes associated with anti-inflammatory macrophages, and upregulated cytokine and marker genes of proinflammatory macrophages in RA. On the other hand, STRMs hardly changed the expression of surface molecules and marker genes but altered the pattern of cytokine gene expression after stimulation like PBMoMs. Furthermore, in vitro stimulated STRMs promote proinflammatory functions of cocultured synovial fibroblasts. Thus, STRMs might play proinflammatory roles in RA joints, while maintaining their phenotypes in the steady state.","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"58-67"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088925","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}

引用次数: 0

Risk of disease flares after SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus. 系统性红斑狼疮患者接种 SARS-CoV-2 mRNA 疫苗后疾病复发的风险。

IF 4.4

Immunological Medicine Pub Date : 2024-06-01 Epub Date: 2024-01-08 DOI: 10.1080/25785826.2023.2300163

Jun Kikuchi, Yasushi Kondo, Shuichiro Kojima, Shiho Kasai, Yuma Sakai, Masaru Takeshita, Kazuoto Hiramoto, Shuntaro Saito, Hiroyuki Fukui, Hironari Hanaoka, Katsuya Suzuki, Yuko Kaneko

{"title":"Risk of disease flares after SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus.","authors":"Jun Kikuchi, Yasushi Kondo, Shuichiro Kojima, Shiho Kasai, Yuma Sakai, Masaru Takeshita, Kazuoto Hiramoto, Shuntaro Saito, Hiroyuki Fukui, Hironari Hanaoka, Katsuya Suzuki, Yuko Kaneko","doi":"10.1080/25785826.2023.2300163","DOIUrl":"10.1080/25785826.2023.2300163","url":null,"abstract":"This study aims to elucidate the effectiveness and safety of SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus (SLE). We enrolled uninfected SLE patients who received two vaccine doses (BNT162b2 or mRNA-1273) and historical unvaccinated patients. Neutralizing antibodies, adverse reactions, and disease flares were evaluated 4 weeks after the second vaccination. Ninety patients were enrolled in each group. Among the vaccinated patients, SLE Disease Activity Index (SLEDAI), and prednisolone doses before vaccination were 2, and 5 mg/d, respectively. After the second vaccination, 19 (21.1%) had no neutralizing antibodies. Adverse reactions occurred in 88.9% within 3 d. Negative antibodies were associated with anemia and mycophenolate mofetil administration. SLEDAI increased modestly but significantly after vaccination, with 13 (14.4%) experiencing flares and 4 (4.4%) severe flares (nephritis in three and vasculitis in one). The flare rate was higher in vaccinated patients than unvaccinated controls. The mean duration between the second vaccination and flares was 35 d, and flares occurred at least 8 days after vaccination. Multivariable analysis showed that high SLEDAI and anti-dsDNA antibodies were associated with flares. The vaccine type, neutralizing antibody titer, and adverse reaction frequency did not affect flares. Therefore, residual disease activity before vaccination increases flare risk.","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"76-84"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378443","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}

引用次数: 0

Prophylactic immunoglobulin therapy for pediatric congenital myotonic dystrophy. 小儿先天性肌营养不良症的预防性免疫球蛋白疗法。

IF 2.7

Immunological Medicine Pub Date : 2024-06-01 Epub Date: 2024-01-25 DOI: 10.1080/25785826.2024.2306672

Yoji Uejima, Satoshi Sato

{"title":"Prophylactic immunoglobulin therapy for pediatric congenital myotonic dystrophy.","authors":"Yoji Uejima, Satoshi Sato","doi":"10.1080/25785826.2024.2306672","DOIUrl":"10.1080/25785826.2024.2306672","url":null,"abstract":"Congenital Myotonic Dystrophy (CMD) is an autosomal dominant hereditary disease caused by mutations in the dystrophia myotonica protein kinase gene. Patients with CMD often exhibit low immunoglobulin (Ig) G levels. While Ig replacement therapy for low IgG levels has been reported in several adult cases, there have been no reports on pediatric patients. This study presents a first pediatric case where Ig replacement therapy effectively eliminated susceptibility to infections. The CMD patient, a 1-year-old Japanese female with a history of premature birth and necrotizing enterocolitis, developed recurrent severe bacterial infections due to hypogammaglobulinemia. Intravenous immunoglobulin (IVIG) (600 mg/kg/month) was administered but failed to maintain sufficient serum trough IgG levels. The dosage was increased to 2 g/kg/month, and later, the treatment shifted to subcutaneous immunoglobulin (SCIG), resulting in a stable serum trough IgG level above 700 mg/dL for one year. The cause of hypogammaglobulinemia in CMD patients remains unclear, but potential mechanisms, including IgG-mediated hypercatabolism by alterations in the neonatal Fc receptor, have been considered. Genetic testing ruled out common variable immunodeficiency, and other potential causes were excluded. The study suggests that higher doses of IVIG or SCIG can effectively prevent severe infections associated with CMD-induced hypogammaglobulinemia in children.","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"106-109"},"PeriodicalIF":2.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545901","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}

引用次数: 0

C5a stimulation induces caspase-1 activation and mature IL-1β production in human peripheral blood mononuclear cells. C5a 刺激可诱导 Caspase-1 活化和人类外周血单核细胞产生成熟的 IL-1β。

IF 4.4

Immunological Medicine Pub Date : 2024-06-01 Epub Date: 2023-12-15 DOI: 10.1080/25785826.2023.2292665

Yuya Fujita, Haruki Matsumoto, Kenji Inada, Michio Onizawa, Kenji Saito, Yuya Sumichika, Shuhei Yoshida, Jumpei Temmoku, Naoki Matsuoka, Tomoyuki Asano, Shuzo Sato, Takeshi Machida, Kiyoshi Migita

{"title":"C5a stimulation induces caspase-1 activation and mature IL-1β production in human peripheral blood mononuclear cells.","authors":"Yuya Fujita, Haruki Matsumoto, Kenji Inada, Michio Onizawa, Kenji Saito, Yuya Sumichika, Shuhei Yoshida, Jumpei Temmoku, Naoki Matsuoka, Tomoyuki Asano, Shuzo Sato, Takeshi Machida, Kiyoshi Migita","doi":"10.1080/25785826.2023.2292665","DOIUrl":"10.1080/25785826.2023.2292665","url":null,"abstract":"The complement component C5a contributes to the recruitment of immune cells to inflamed tissues and local inflammation. The proinflammatory cytokine interleukin (IL)-1β is also related to inflammatory disorders through inflammasome activation. However, the association between inflammasome activation and C5a is unclear. Human peripheral blood mononuclear cells (PBMCs) were stimulated with C5a and measured for IL-1β secretion by enzyme-linked immunosorbent assay (ELISA). The pro-IL-1β expression in cell lysates was also examined by Western blot analysis. Similarly, magnetic bead-isolated CD14+ monocyte-depleted and lymphocyte-depleted PBMCs were stimulated with C5a, and immunoblot analysis was performed using an anti-cleaved-IL-1β (p17) antibody. FACS was performed to detect caspase-1-activated cells. C5a-stimulated PBMCs produced IL-1β in C5a concentration-dependent manner. The protein levels of pro-IL-1β in the cell lysates were significantly increased. Furthermore, the cleaved-IL-1β (p17) was faintly detected in the same lysates. Active caspase-1 was demonstrated in C5a-simulated CD14+ monocytes by FACS. Cleaved-IL-1β (p17) was demonstrated in the supernatant of C5a-stimulated PBMCs. Lymphocyte-depleted PBMCs stimulated with C5a but monocyte-depleted PBMCs produced cleaved-IL-1β (p17). C5a induced the production of mature IL-1β in PBMCs. The IL-1β production is mediated mainly by caspase-1 activation in CD14+ monocytes. These results suggest that C5a alone potentiates mature IL-1β production mainly in monocytes.","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"68-75"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138811111","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}

引用次数: 0

Pathophysiology and stratification of treatment-resistant rheumatoid arthritis. 抗药性类风湿性关节炎的病理生理学和分层。

IF 4.4

Immunological Medicine Pub Date : 2024-03-01 Epub Date: 2023-07-18 DOI: 10.1080/25785826.2023.2235734

Saeko Yamada, Yasuo Nagafuchi, Keishi Fujio

{"title":"Pathophysiology and stratification of treatment-resistant rheumatoid arthritis.","authors":"Saeko Yamada, Yasuo Nagafuchi, Keishi Fujio","doi":"10.1080/25785826.2023.2235734","DOIUrl":"10.1080/25785826.2023.2235734","url":null,"abstract":"Early diagnosis and timely therapeutic intervention are clinical challenges of rheumatoid arthritis (RA), especially for treatment-resistant or difficult-to-treat patients. Little is known about the immunological mechanisms involved in refractory RA. In this review, we summarize previous research findings on the immunological mechanisms of treatment-resistant RA. Genetic prediction of treatment-resistant RA is challenging. Patients with and without anti-cyclic citrullinated peptide autoantibodies are considered part of distinct subgroups, especially regarding long-term clinical prognosis and treatment responses. B cells, T cells and other immune cells and fibroblasts are of pathophysiological importance and are associated with treatment responses. Finally, we propose a new hypothesis that stratifies patients with RA into two subgroups with distinct immunological pathologies based on our recent immunomics analysis of RA. One RA subgroup with a favorable prognosis is characterized by increased interferon signaling. Another subgroup with a worse prognosis is characterized by enhanced acquired immune responses. Increases in dendritic cell precursors and diversified autoreactive anti-modified protein antibodies may have pathophysiological roles, especially in the latter subgroup. These findings that improve treatment response predictions might contribute to future precision medicine for RA.","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"12-23"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185867","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}

引用次数: 0

A new therapeutic target for systemic lupus erythematosus: the current landscape for drug development of a toll-like receptor 7/8 antagonist through academia-industry-government collaboration. 系统性红斑狼疮的一个新的治疗靶点：通过学术界-行业-政府合作开发toll样受体7/8拮抗剂的当前前景。

IF 4.4

Immunological Medicine Pub Date : 2024-03-01 Epub Date: 2023-09-29 DOI: 10.1080/25785826.2023.2264023

Yoshiya Tanaka, Fumitoshi Tago, Naoto Yamakawa, Mari Aoki, Takuya Yagi, Shizuo Akira

{"title":"A new therapeutic target for systemic lupus erythematosus: the current landscape for drug development of a toll-like receptor 7/8 antagonist through academia-industry-government collaboration.","authors":"Yoshiya Tanaka, Fumitoshi Tago, Naoto Yamakawa, Mari Aoki, Takuya Yagi, Shizuo Akira","doi":"10.1080/25785826.2023.2264023","DOIUrl":"10.1080/25785826.2023.2264023","url":null,"abstract":"Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by inflammation in multiple organs. A few treatments for SLE currently exist, including antimalarials, glucocorticoids, immunosuppressants, and two recently approved antibody agents; however, an unmet medical need remains for SLE. In addition, developing new drugs targeting SLE is a challenge since no specific biomarkers exist for the prediction of disease progression or drug response. A new drug candidate, E6742, is a specific antagonist of the toll-like receptors 7/8. To address the challenges for drug development in SLE, the process of developing E6742 utilizes a unique system of the Japan Agency for Medical Research and Development (AMED), the Cyclic Innovation for Clinical Empowerment (CiCLE) program. In the CiCLE program, a Phase 1 study in healthy adults was completed (NCT04683185) and a Phase 1/2 study in patients with SLE is on-going (NCT05278663). One of the potential benefits of this program is to conduct academia-led clinical research to identify specific biomarkers for E6742 in parallel with clinical studies (UMIN000042037). The aim of this review is to present current progress within the strategic collaboration of the AMED CiCLE program that optimize clinical development for patients with SLE.","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"24-29"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41146837","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}

引用次数: 0