Immunological Medicine最新文献

{"title":"Anti-cytokine autoantibodies in human susceptibility to infectious diseases: insights from Inborn errors of immunity.","authors":"Kosuke Noma, Takaki Asano, Maki Taniguchi, Kosuke Ashihara, Satoshi Okada","doi":"10.1080/25785826.2025.2488553","DOIUrl":"https://doi.org/10.1080/25785826.2025.2488553","url":null,"abstract":"<p><p>The study of Inborn Errors of Immunity (IEIs) is critical for understanding the complex mechanisms of the human immune response to infectious diseases. Specific IEIs, characterized by selective susceptibility to certain pathogens, have enhanced our understanding of the key molecular pathways and cellular subsets involved in host defense against pathogens. These insights revealed that patients with anti-cytokine autoantibodies exhibit phenotypes similar to those with pathogenic mutations in genes encoding signaling molecules. This new disease concept is currently categorized as 'Phenocopies of IEI'. This category includes anti-cytokine autoantibodies targeting IL-17/IL-22, IFN-γ, IL-6, GM-CSF, and type I IFNs. Abundant anti-cytokine autoantibodies deplete corresponding cytokines, impair signaling pathways, and increase susceptibility to specific pathogens. We herein demonstrate the clinical and etiological significance of anti-cytokine autoantibodies in human immunity to pathogens. Insights from studies of rare IEIs underscore the pathological importance of cytokine-targeting autoantibodies. Simultaneously, the diverse clinical phenotype of patients with these autoantibodies suggests that the influences of cytokine dysfunction are broader than previously recognized. Furthermore, comprehensive studies prompted by the COVID-19 pandemic highlighted the substantial clinical impact of autoantibodies and their potential role in shaping the outcomes of infectious disease.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804411","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":"Bibliometric analysis of systemic lupus erythematosus during pregnancy from 2003 to 2024.","authors":"Xinyan Zou, Xinfu Zou, Qiaoqiao Liu, Bingxin Zhou, Shujie He, Xiulan Liao, Hanqing Zhao","doi":"10.1080/25785826.2025.2483811","DOIUrl":"https://doi.org/10.1080/25785826.2025.2483811","url":null,"abstract":"<p><p>Autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome have a significant impact on pregnancy, potentially exacerbating SLE symptoms and leading to miscarriage, pre-eclampsia and other pregnancy complications. To ensure the safety of SLE patients during pregnancy, experts have conducted in-depth research and provided recommendations. Therefore, it is necessary to provide a thorough summary of the current status, hotspots and emerging trends in this research field. We systematically searched the Web of Science Core Collection database for studies on SLE during pregnancy from 1 January 2003 to 24 March 2024. We then utilized CiteSpace to generate a knowledge visualization map. This analysis included a total of 2239 studies on SLE during pregnancy. The yearly volume of publications exhibits a persistent increasing trend. The United States had the highest number of publications and was the leading country, while the Czech Republic had the highest centrality and influence. The research focused on three main areas: (1) pregnancy outcomes in autoimmune diseases, (2) newborn-related diseases and complications and (3) medication management for patients with SLE during pregnancy. Our study offers both a visual and scientific synopsis of research concerning SLE during pregnancy, furnishing valuable insights and opening up new avenues for researchers.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731955","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":"Systemic sclerosis presenting TAFRO syndrome-like manifestations including renal glomerular microangiopathy: a case report and literature review.","authors":"Hiroyuki Kawahara, Satoshi Hara, Noriko Iwaki, Hiroko Ikeda, Dai Inoue, Ichiro Mizushima, Hideki Nomura, Yasufumi Masaki, Yasunori Iwata, Mitsuhiro Kawano","doi":"10.1080/25785826.2025.2481675","DOIUrl":"https://doi.org/10.1080/25785826.2025.2481675","url":null,"abstract":"<p><p>TAFRO syndrome is a systemic inflammatory disorder of unknown etiology, and its diagnosis requires the exclusion of autoimmune diseases. A 42-year-old Japanese woman presented with TAFRO syndrome-like manifestations, but had undiagnosed limited-cutaneous systemic sclerosis preventing a definitive diagnosis of TAFRO syndrome. However, her clinical course and pathological findings, including renal glomerular microangiopathy, were consistent with TAFRO syndrome. We performed a systematic review of the literature to evaluate how autoimmunity affects the clinical characteristics of TAFRO syndrome/idiopathic multicentric Castleman disease (iMCD)-TAFRO. We reviewed 95 reported cases of TAFRO syndrome/iMCD-TAFRO and found that at least 41 (43.6%) had various autoantibodies. In particular, the positive rates of anti-nuclear antibody, anti-SS-A antibody, anti-SS-B antibody, PA-IgG, and direct Coombs test were high. Furthermore, we identified 14 cases of autoimmune diseases with TAFRO syndrome-like manifestations. We compared the clinical characteristics of these 14 with those of the autoantibody-positive and -negative cases among the 95 cases of TAFRO syndrome/iMCD-TAFRO. Apart from sex ratio, we found no significant difference in clinical presentation, treatment, or outcome among the groups. In conclusion, TAFRO syndrome/iMCD-TAFRO often accompanies autoantibodies and shares many clinical characteristics with other autoimmune diseases. Clinicians should be aware that some autoimmune diseases mimic TAFRO syndrome/iMCD-TAFRO.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-10"},"PeriodicalIF":2.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674660","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":"Overlapping Aicardi-Goutières and Singleton-Merten syndromes with a heterozygous gain-of-function mutation in <i>IFIH1</i> mimicking juvenile idiopathic arthritis.","authors":"Susumu Yamazaki, Shuya Kaneko, Asami Shimbo, Hitoshi Irabu, Ryo Ogino, Takayuki Miyamoto, Kazushi Izawa, Yuko Segawa, Jun Kakizaki, Masaaki Mori, Masaki Shimizu","doi":"10.1080/25785826.2025.2479148","DOIUrl":"https://doi.org/10.1080/25785826.2025.2479148","url":null,"abstract":"<p><p>Aicardi-Goutières syndrome (AGS) and Singleton-Merten syndrome (SMS) are associated with heterozygous gain-of-function mutations in the interferon induced with helicase C domain 1 (IFIH1) gene. Recent reports describe patients exhibiting overlapping clinical features of AGS and SMS, along with marked type I interferon (IFN) overproduction. However, the clinical characteristics and optimal treatment strategies remain unclear. Herein, we present a patient with overlapping clinical features of AGS and SMS who was initially misdiagnosed with juvenile idiopathic arthritis. Surgical soft tissue release of the hip and knee joints improved joint deformities and spastic paraparesis. Baricitinib effectively treated refractory chilblains and skin ulcers while reducing IFN-stimulated gene overexpression in peripheral blood. These findings indicate that baricitinib may be a safe and effective treatment for AGS-SMS overlap, and surgical intervention may be a viable option for refractory joint deformities with spastic paraparesis.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-5"},"PeriodicalIF":2.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674590","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":"When ocular surface treatment fails: exploring neuropathic ocular pain in aqueous-deficient dry eye due to Sjögren's syndrome treated with mirogabalin: a case study.","authors":"Yoshiaki Tagawa, Yusuke Aihara, Susumu Ishida","doi":"10.1080/25785826.2025.2477321","DOIUrl":"https://doi.org/10.1080/25785826.2025.2477321","url":null,"abstract":"<p><p>Dry eye disease can be classified as aqueous-deficient, evaporative and mixed-type. Recently, neuropathic pain has been indicated to be involved in the subjective symptoms of aqueous-deficient dry eye. However, the mechanism underlying neuropathic ocular pain in such patients remains elusive. Here, we present the case of a patient with aqueous-deficient dry eye disease and severe corneal and conjunctival epithelial damage due to Sjögren's syndrome. Despite considerable improvements in ocular surface conditions with local treatments, such as punctal plugs, autologous serum eye drops, rebamipide eye drops, and tacrolimus eye drops, the patient experienced severe ocular pain for two years, which was disproportionate to the objective clinical findings. The pain worsened during the exacerbations of systemic symptom, such as arthritis and interstitial pneumonia, without correlating with the ocular surface findings. The administration of mirogabalin, a neuropathic pain medication, effectively alleviated the patient's subjective ocular pain symptoms. Ocular pain in patients with Sjögren's syndrome is not necessarily linked to an aqueous deficiency or ocular surface findings. It can arise as neuropathic ocular pain due to inflammation spreading to the trigeminal nerve. Given the systemic inflammatory condition and characteristics of the ocular pain, administering neuropathic pain medications should be considered as a treatment option.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-5"},"PeriodicalIF":2.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650820","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":"Advances in understanding the role and mechanism of the cGAS-STING signaling pathway in ocular diseases.","authors":"MengDi Zhang, Jiayu Xu, Wenjia Qu, Jia Gao, Ya Mo","doi":"10.1080/25785826.2025.2475626","DOIUrl":"https://doi.org/10.1080/25785826.2025.2475626","url":null,"abstract":"<p><p>The cGAS-STING signaling pathway plays a critical role in the immune defense against DNA viruses and in autoimmunity, coordinating a cascade of events that enhance cytokine production, particularly type I interferons. This review summarizes recent advancements in understanding the pathway's impact on various ocular diseases, including age-related macular degeneration (AMD), diabetic retinopathy, and uveitis. Activation of this pathway by cytoplasmic DNA from either damaged retinal cells or external pathogens induces inflammatory responses that may accelerate disease progression. Moreover, the paper explores new therapeutic approaches that target this pathway, offering insights into how modulation of cGAS-STING signaling could reduce inflammation and improve clinical outcomes. The emerging research in this area suggests potential for innovative treatments in ocular inflammation and degenerative conditions.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587544","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":"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":" ","pages":"33-46"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","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":"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":"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":" ","pages":"89-93"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","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}

{"title":"Investigating the impact of tocilizumab on serum cytokines concentrations in Japanese FMF patients: a sub-analysis of the NUH01FMF study.","authors":"Tomohiro Koga, Shuntaro Sato, Kaori Furukawa, Hiroshi Yamamoto, Atsushi Kawakami","doi":"10.1080/25785826.2024.2418164","DOIUrl":"10.1080/25785826.2024.2418164","url":null,"abstract":"<p><p>Familial Mediterranean Fever (FMF) is the most common hereditary autoinflammatory disease, characterized by recurrent fever, arthritis, rash, and serositis, and is caused by mutations in the MEFV gene coding for the pyrin protein. The primary treatment goal is to prevent acute attacks and minimize subclinical inflammation to avoid secondary amyloidosis with colchicine as the first-line treatment. However, 10-20% of patients are colchicine-resistant or intolerant. While the therapeutic potential of IL-6 inhibitors such as tocilizumab (TCZ) has been suggested, the detailed serum cytokine profiles after TCZ treatment in patients with FMF remain largely unexplored. This study focused on a sub-analysis of a clinical trial evaluating TCZ in patients with colchicine-resistant FMF (crFMF). We analyzed the serum cytokine profiles at 0, 2, 4, 8, 12, 16, 20, and 24 weeks in the TCZ and placebo groups. Our findings revealed a decrease in serum C-X-C motif chemokine ligand 1 and vascular endothelial growth factor levels in the TCZ group at week 4 compared to baseline, which persisted until week 24, indicating the potential of TCZ to manage crFMF by modulating specific inflammatory cytokines. Further research is required to confirm these findings and optimize the treatment strategies for FMF.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"70-77"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509810","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":"Increased response to granulocyte-macrophage colony-stimulating factor in peripheral blood cells and transient manifestations mimicking juvenile myelomonocytic leukemia in a male patient with NEMO deficiency caused by a deep intronic pathogenic variant of IKBKG.","authors":"Masahiro Ueki, Shinsuke Hirabayashi, Yoshitaka Honda, Shunichiro Takezaki, Hiroki Ohata, Shimaa Said Mohamed Ali Abdrabou, Saori Sawai, Yukayo Terashita, Yuko Cho, Hideki Muramatsu, Kazushi Izawa, Takahiro Yasumi, Yoshiyuki Takahashi, Masafumi Yamada, Atsushi Manabe","doi":"10.1080/25785826.2024.2422639","DOIUrl":"10.1080/25785826.2024.2422639","url":null,"abstract":"<p><p>X-linked NF-κB essential modulator (NEMO) deficiency is a primary immunodeficiency characterized by combined immunodeficiency and ectodermal dysplasia. Monocytes from the patients demonstrate a severely impaired response to tissue necrosis factor or lipopolysaccharide, whereas hyper-inflammation is found in some patients. Juvenile myelomonocytic leukemia (JMML) is a pediatric malignancy caused by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) and aberrant RAS signaling activation. Patients with JMML demonstrate characteristic manifestations such as splenomegaly, monocytosis and the presence of myeloid or erythroid precursors in the peripheral blood. Here, we present the case of a male infant with ectodermal dysplasia, bacterial septicemia, Pneumocystis pneumonia, severe inflammation and transient manifestations mimicking JMML. Genetic analysis revealed a deep intronic germline variant of IKBKG. Full-length IKBKG cDNA and NEMO protein expression were almost inexistent. Peripheral mononuclear cells (PBMCs) from the patient showed increased RAS signaling activation with GM-CSF or Phorbol 12-myristate 13-acetate without the RAS-associated gene variant, although the increased RAS signaling activation in induced-pluripotent stem cell-derived myeloid lineage and bone marrow-derived mesenchymal cells was not evident. The patient with NEMO deficiency demonstrated JMML-like manifestation and severe inflammation. PBMCs of the patient demonstrated increased RAS signaling activation with unknown pathophysiology.</p>","PeriodicalId":37286,"journal":{"name":"Immunological Medicine","volume":" ","pages":"94-101"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559067","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}