Jagoda Siemaszko, Piotr Łacina, Donata Szymczak, Agnieszka Szeremet, Maciej Majcherek, Anna Czyż, Małgorzata Sobczyk-Kruszelnicka, Wojciech Fidyk, Iwona Solarska, Barbara Nasiłowska-Adamska, Patrycja Skowrońska, Maria Bieniaszewska, Agnieszka Tomaszewska, Grzegorz W Basak, Sebastian Giebel, Tomasz Wróbel, Katarzyna Bogunia-Kubik
{"title":"ILT-2 and ILT-4 expression and donor genotype as factors associated with HSCT outcome.","authors":"Jagoda Siemaszko, Piotr Łacina, Donata Szymczak, Agnieszka Szeremet, Maciej Majcherek, Anna Czyż, Małgorzata Sobczyk-Kruszelnicka, Wojciech Fidyk, Iwona Solarska, Barbara Nasiłowska-Adamska, Patrycja Skowrońska, Maria Bieniaszewska, Agnieszka Tomaszewska, Grzegorz W Basak, Sebastian Giebel, Tomasz Wróbel, Katarzyna Bogunia-Kubik","doi":"10.1016/j.clim.2025.110605","DOIUrl":"10.1016/j.clim.2025.110605","url":null,"abstract":"<p><strong>Background: </strong>NK cell activity after allogeneic haematopoietic stem cell transplantation (HSCT) is still not fully understood. Their cytotoxic activity is modulated by a range of inhibitory and activating surface receptors. Among these, the inhibitory receptors ILT-2 and ILT-4 have yet to be explored in relation to HSCT and its outcomes.</p><p><strong>Methods: </strong>Genotyping for ILT-2 and ILT-4 was performed using TaqMan assays. ILT-2 and ILT-4 surface expression on NK cells was assessed by flow cytometry. Levels of sHLA-F and sHLA-G were determined using ELISA. mRNA expression of ILT-2, ILT-4 and IFN-γ was measured with quantitative real-time PCR with TaqMan Gene Expression probes.</p><p><strong>Results: </strong>Presence of donor ILT-2 rs1061681 T allele was associated with increased risk of chronic graft-versus-host disease (cGVHD) (p = 0.0239). Donor ILT-4 rs1128646 T allele was related with decreased risk of overall survival after HSCT (p = 0.0506) and with higher risk of acute GvHD (aGvHD) (p = 0.0834). Serum levels of sHLA-F and sHLA-G were significantly higher at day +30 than day +90 after HSCT (p = 0.0002 and p < 0.0001, respectively). Expression of ILT2 at mRNA level was significantly decreased among recipients with aGvHD (p = 0.0266). ILT-4 expression correlated negatively with expression of interferon gamma (p = 0.0280, R = -0.532). The percentages of LILRB1/ILT-2+ and LILRB2/ILT4+ NK cells were the highest at day +21 after HSCT (p = 0.0014 and p < 0.0001 for ILT-2 and ILT-4, respectively).</p><p><strong>Conclusions: </strong>Both ILT-2 and ILT-4 inhibitory receptors were found to be associated with allogeneic HSCT outcome. This suggests that ILT receptor expression on NK cells may potentially play a role in post-transplant complications.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110605"},"PeriodicalIF":3.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regarding the “Efgartigimod versus standard of care in new-onset AChR subtype generalized myasthenia gravis: A prospective cohort study”","authors":"Hai-Feng Li , Shi-Min Hu , Wei Han , Yan-Su Guo","doi":"10.1016/j.clim.2025.110603","DOIUrl":"10.1016/j.clim.2025.110603","url":null,"abstract":"","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110603"},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Youmna El-Orfali , Hagop Mardirossian , Habib Al-Kalamouni , Zeinab El-Zein , Samar Dalle , Dima Khreis , Amani Haddara , Rima Hanna-Wakim , Ghassan Dbaibo , Michel J. Massaad
{"title":"Clinical, biochemical, and genetic characterization of Lebanese patients with chronic granulomatous disease due to NCF2 pathogenic variants","authors":"Youmna El-Orfali , Hagop Mardirossian , Habib Al-Kalamouni , Zeinab El-Zein , Samar Dalle , Dima Khreis , Amani Haddara , Rima Hanna-Wakim , Ghassan Dbaibo , Michel J. Massaad","doi":"10.1016/j.clim.2025.110596","DOIUrl":"10.1016/j.clim.2025.110596","url":null,"abstract":"<div><div>Chronic Granulomatous Disease (CGD) is caused by mutations in the NADPH oxidase complex that impair the ability of phagocytes to eliminate injested pathogens. As a result, patients with CGD suffer from recurrent infections and chronic inflammation. We report the clinical, biochemical, and genetic basis of the disease in 17 CGD patients from Lebanon. Whole exome sequencing (WES) identified 2 distinct mutations in <em>NCF2</em> resulting in the deletion of exons 3 and 5, accounting for 82 % of the cases that underwent WES. This high prevalence provided the rationale for a diagnostic strategy involving assessment of NADPH oxidase function, identification of the affected protein, and targeted gene sequencing. Using this approach, 3 additional CGD patients with simmilar deletions were identified, supporting the presence of a founder effect in the Lebanese population. This biochemical and tageted sequencing approach is rapid, reliable, and cost-effective, making it a particularly valuable diagnostic option for families who cannot afford WES.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110596"},"PeriodicalIF":3.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Primary immunodeficiency diseases, inflammation and mitochondrial dysfunction","authors":"Salvatore Nesci , Francesca Oppedisano , Giovanni Romeo , Silvia Granata","doi":"10.1016/j.clim.2025.110595","DOIUrl":"10.1016/j.clim.2025.110595","url":null,"abstract":"<div><div>Primary immunodeficiency diseases (PIDs) are a heterogeneous group of inherited disorders characterized by impaired immune function, leading to increased susceptibility to infections, autoimmunity, and malignancies. While traditionally defined by immune cell defects, emerging evidence highlights the critical role of inflammation in PID pathogenesis. This review explores the intricate relationship between mitochondrial dysfunction and inflammation in PIDs. We examine how genetic defects in PIDs disrupt immune homeostasis, promoting pro-inflammatory states through cytokine dysregulation. Additionally, we discuss the vicious cycle involving oxidative stress, mitochondrial dysfunction, and inflammation, emphasizing the contribution of mitochondrial ROS production, mtDNA damage, and inflammasome activation in sustaining chronic inflammation. Furthermore, we propose that impaired mitochondrial function —potentially through mechanisms involving calcium signalling, ATP synthase regulation, and mitochondrial permeability transition pore formation — may serve as a central link between immune deficiency and hyperinflammation in PIDs. Understanding these complex interactions may provide new insights into the pathogenesis of PIDs and open avenues for targeted therapeutic strategies to improve patient outcomes.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110595"},"PeriodicalIF":3.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu-Jie Zhan , Wei Liu , Bu-Yi Wang , Bo-Yang Ma , Jia-Ye Wang , Yi-Lin Zhao , Xin-Xin Wang , Yue Jiang , Dan Wang , Li Wang , Hong Ling , Min Zhuang
{"title":"B cell receptor repertoires identified by next-generation sequencing showed signatures associated with incomplete immune reconstitution in people living with HIV","authors":"Yu-Jie Zhan , Wei Liu , Bu-Yi Wang , Bo-Yang Ma , Jia-Ye Wang , Yi-Lin Zhao , Xin-Xin Wang , Yue Jiang , Dan Wang , Li Wang , Hong Ling , Min Zhuang","doi":"10.1016/j.clim.2025.110594","DOIUrl":"10.1016/j.clim.2025.110594","url":null,"abstract":"<div><div>Incomplete immune reconstitution poses a significant challenge for anti-retroviral therapy (ART) in HIV-infected individuals. The role of B cell receptors (BCRs) in immune reconstitution, a critical aspect of the immune system, has not been well elucidated in ART-experienced people. We analyzed the BCR heavy chain repertoire in immune non-responders (INRs) and immune responders (IRs) by next-generation sequencing. The BCR repertoire of INRs was characterized by a higher proportion of longer HCDR3 and reduced frequencies of IGHV1–69, IGHJ2, and IGHV1–69/IGHJ4 and IGHV5–51/IGHJ4 pairings. INRs, rather than IRs, carried HCDR3 genes which were highly homologous to anti-HIV broadly neutralizing antibodies targeting the six-helix bundle (6HB) in envelope gp41. The plasmas of INRs also exhibited an increased reactivity to FPPR-N36, a peptide within 6HB. These findings indicated a potential association between BCR, antibodies to partial gp41, and incomplete immune reconstitution and provided new perspectives for understanding the BCR repertoire and immune reconstitution.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110594"},"PeriodicalIF":3.8,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alanna M. Kelly , Emilio G. Vozza , Brenda Morris , Seán C. Cahill , Charlotte M. Leane , Sinéad C. Corr , Rachel M. McLoughlin
{"title":"Staphylococcus aureus induces miR-21 expression to promote bacterial persistence during nasal colonisation","authors":"Alanna M. Kelly , Emilio G. Vozza , Brenda Morris , Seán C. Cahill , Charlotte M. Leane , Sinéad C. Corr , Rachel M. McLoughlin","doi":"10.1016/j.clim.2025.110593","DOIUrl":"10.1016/j.clim.2025.110593","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> nasal colonisation is commonplace among healthy individuals, yet the immune mechanisms enabling bacterial persistence remain unclear. <em>S. aureus</em> drives local immunosuppression during nasal colonisation to facilitate persistence. This study reveals that <em>S. aureus</em> subverts microRNA-21 activity to promote IL-10 production within nasal tissue, while simultaneously impeding local pro-inflammatory responses. MiR-21 activity helps establish a <em>S. aureus</em>-induced immunosuppressive microenvironment, which supports <em>S. aureus</em> persistence. Macrophages, which are key IL-10 producers, rapidly upregulate miR-21 upon <em>S. aureus</em> exposure. MiR-21 expression also coincides with an increase in intracellular survival of <em>S. aureus</em> within macrophages. Furthermore, <em>S. aureus</em> represses macrophage glycolysis to promote intracellular survival, which is dependent upon miR-21. Upon <em>S. aureus</em> colonisation, miR-21<sup>−/−</sup> mice demonstrate an overall improved bacterial clearance compared to their wild-type counterparts. These findings highlight the targeting of miR-21, which controls glycolytic activity in macrophages, as a potential avenue to reducing bacterial persistence during <em>S. aureus</em> colonisation.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110593"},"PeriodicalIF":3.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sha-Sha Tao , Hai-Fen Wei , Shu-Zhen Xu , Xiao-Xiao Li , Yan-Yu Zhu , Jian Tang , Wen-Jie Li , Yu-Wan Chang , Zhu Chen , Hai-Feng Pan
{"title":"LncRNA MEG3 as a biomarker and therapeutic target in rheumatoid arthritis: Insights from gene polymorphisms, expression patterns, and functional mechanisms","authors":"Sha-Sha Tao , Hai-Fen Wei , Shu-Zhen Xu , Xiao-Xiao Li , Yan-Yu Zhu , Jian Tang , Wen-Jie Li , Yu-Wan Chang , Zhu Chen , Hai-Feng Pan","doi":"10.1016/j.clim.2025.110590","DOIUrl":"10.1016/j.clim.2025.110590","url":null,"abstract":"<div><div>Maternally expressed gene 3 (<em>MEG3</em>) is implicated in autoimmunity, but its role in rheumatoid arthritis (RA) is unclear. This study aimed to investigate gene polymorphisms, expression patterns, and functional mechanisms of <em>MEG3</em> in RA pathogenesis and its clinical associations. <em>MEG3</em> single nucleotide polymorphisms (SNPs) were genotyped in 551 RA patients and 595 controls, finding no association with RA susceptibility. <em>MEG3</em> expression was downregulated in peripheral blood mononuclear cells (PBMCs) from RA patients, particularly in ACPA-positive cases, but increased with NSAID use. In fibroblast-like synoviocytes (FLS), <em>MEG3</em> was downregulated. Overexpression of <em>MEG3</em> inhibited FLS proliferation and invasion, lowering IL-1β and IL-6 but not TNF-α. Whereas <em>MEG3</em> knockdown enhanced FLS proliferation and invasion, elevating TNF-α and IL-1β without altering IL-6. Collectively, <em>MEG3</em> polymorphisms are not associated with RA susceptibility. <em>MEG3</em> dysregulation correlates with RA clinical indicators and regulates FLS pathogenicity, indicating its potential as a clinical biomarker and therapeutic target in RA.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110590"},"PeriodicalIF":3.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of immune complex antigens that are detected prior to early rheumatoid arthritis symptoms and increase with disease progression: Comprehensive serum immune complexome analysis to identify candidate disease biomarkers in health checkup cohort study","authors":"Yuki Jimbayashi Kutsuna , Nozomi Aibara , Junya Hashizume , Sayaka Kawarabayashi , Mami Tamai , Jun Miyata , Hajime Yoshifuji , Hirotaka Miyamoto , Kayoko Sato , Yukinobu Kodama , Mikiro Nakashima , Atsushi Kawakami , Takahiro Maeda , Kaname Ohyama","doi":"10.1016/j.clim.2025.110591","DOIUrl":"10.1016/j.clim.2025.110591","url":null,"abstract":"<div><div>Although anti-cyclic citrullinated peptide is a biomarker, its contribution to rheumatoid arthritis pathogenesis is unknown, and it has not been a therapeutic target to date. As inflammatory pathology is present from an early stage, and increased immune complexes have been suggested to contribute to pathogenesis, we investigated the presence of disease-related antigens that form immune complexes that increase in abundance with disease progression. Using immune complexome analysis, we analyzed immune complex antigen to disease progression for very-early rheumatoid arthritis (<em>n</em> = 52) and early rheumatoid arthritis (<em>n</em> = 19), in comparison with healthy controls (<em>n</em> = 28). Very-early rheumatoid arthritis was defined as those positive for anti-cyclic citrullinated peptide antibody who did not fulfill the diagnostic criteria for rheumatoid arthritis. Seven antigens increased with disease progression and were detected at significantly higher abundance in early rheumatoid arthritis than in other major autoimmune diseases. Among these, three antigens have previously reported associations with rheumatoid arthritis pathogenesis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110591"},"PeriodicalIF":3.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dong-Yeon Kim , Green Kim , Taehwan Oh , YoungMin Woo , Bon-Sang Koo , Seung Ho Baek , Eun-Ha Hwang , Gukhui Min , You Jung An , Jinyoung Won , Youngjeon Lee , Kyung Seob Lim , Yujin Kim , Choong-Min Ryu , Victor Nizet , Jung Joo Hong
{"title":"Structural and functional characteristics of local immune memory formation in SARS-CoV-2-infected cynomolgus macaques","authors":"Dong-Yeon Kim , Green Kim , Taehwan Oh , YoungMin Woo , Bon-Sang Koo , Seung Ho Baek , Eun-Ha Hwang , Gukhui Min , You Jung An , Jinyoung Won , Youngjeon Lee , Kyung Seob Lim , Yujin Kim , Choong-Min Ryu , Victor Nizet , Jung Joo Hong","doi":"10.1016/j.clim.2025.110589","DOIUrl":"10.1016/j.clim.2025.110589","url":null,"abstract":"<div><div>As the primary interface with the environment, the lungs require a robust local immune defense against pathogens. In a non-human primate model of SARS-CoV-2 Omicron infection, we used scRNA-seq, spatial transcriptomics, and immunoassays to investigate localized immune memory. Our results demonstrated established adaptive responses in lung tissue and medLNs, with significant activation of tissue-resident T cells and GC (germinal center) B cells. Inducible bronchus-associated lymphoid tissue (iBALT) formed a functional tertiary lymphoid structure, suggesting potential involvement in local immune responses. These findings highlight the pivotal role of local immunity in preventing re-infection and can facilitate targeted mucosal vaccine development.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110589"},"PeriodicalIF":3.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pocapavir treatment of enterovirus encephalitis in a patient with X-linked Agammaglobulinemia","authors":"Annarosa Soresina , Jessica Galli , Irene Bellicini , Silvia Gambara , Rosaria Scaduto , Sara Roversi , Alessandra Tozzo , Nardo Nardocci , Lorenzo Pinelli , Jeff Hincks , Elisa Fazzi , Raffaele Badolato","doi":"10.1016/j.clim.2025.110592","DOIUrl":"10.1016/j.clim.2025.110592","url":null,"abstract":"<div><div>We report the case of a young boy with X-linked agammaglobulinemia (XLA) who developed progressive gait instability and postural difficulties. Initial cerebrospinal fluid (CSF) analyses and viral PCR testing were negative; however, a brain biopsy confirmed chronic enteroviral encephalitis. The patient was treated with two compassionate-use cycles of pocapavir, in combination with ongoing high-dose intravenous immunoglobulin (IVIG) therapy. Treatment was well tolerated and led to partial neurological improvement followed by clinical stabilization. This case highlights the diagnostic challenges of enteroviral encephalitis in immunocompromised patients and suggests that investigational antivirals such as pocapavir may offer therapeutic benefit in selected cases.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110592"},"PeriodicalIF":3.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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