American journal of clinical and experimental immunology最新文献

{"title":"Comparison of allergen types and complete blood count in pediatric allergic rhinitis.","authors":"Li Liu, Xiangqian Qiu, Shengli Gao, Qingxiang Zeng, Jing Ma, Wenlong Liu","doi":"10.62347/ZYJP2226","DOIUrl":"10.62347/ZYJP2226","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis (AR) is a highly prevalent immunoglobulin E (IgE)-mediated disease that significantly impacts quality of life. While hematological parameters (complete blood count [CBC]) are linked to inflammation in adult AR, their relevance to pediatric populations remains unclear. This study aimed to characterize allergen sensitization profiles, CBC parameters, and immunoglobulin features in pediatric AR patients across demographic subgroups (sex, age, disease duration).</p><p><strong>Methods: </strong>A retrospective study included 253 children with AR (aged 3-12 years; 176 males, 77 females) who tested positive for specific IgE (sIgE) to one or more inhalant allergens (≥ 0.35 IU/mL). Demographics, symptom scores (nasal/ocular), family history, sIgE, CBC, total immunoglobulin E (tIgE), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and complement component 4 (C4) were assessed. Statistical analyses were performed to compare groups based on sex, age (preschool vs. school-age), and disease duration, and to examine correlations between parameters and symptom scores.</p><p><strong>Results: </strong>House dust mites (HDM) (including <i>Dermatophagoides farinae</i> [D. <i>farinae</i>]: 98.81% and <i>Dermatophagoides pteronyssinus</i> [D. <i>pteronyssinus</i>]: 97.63%) were the predominant sensitizing allergens, predominantly with high-grade sensitization (classes 3-6). Males exhibited significantly higher tIgE, D. <i>farinae</i> sIgE, D. <i>pteronyssinus</i> sIgE, German cockroach sIgE, IgA, C4, neutrophils, monocytes, red blood cell (RBC) count, red cell distribution width-coefficient of variation (RDW-CV), and mean corpuscular volume (MCV) compared to females. School-age children and those with longer disease duration had higher HDM sensitization rates (classes 3-6), Total Nasal Symptom Score (TNSS), IgG, IgA, neutrophils, and specific platelet indices (mean platelet volume [MPV], platelet-large cell ratio [P-LCR]), but lower eosinophils compared to preschoolers or those with short disease duration. Eosinophils, basophils, neutrophils, platelets, tIgE, HDM-sIgE, IgA, hematocrit (HCT), and red cell distribution width-standard deviation (RDW-SD) correlated significantly with nasal symptom scores. After adjusting for multiple comparisons and confounding factors, IgA remained independently associated with longer disease duration and showed significant correlations with nasal symptom scores.</p><p><strong>Conclusion: </strong>HDM are the primary allergens in the pediatric AR population in Guangzhou. Significant sex-, age-, and duration-related differences exist in sensitization patterns and immune and CBC profiles. After rigorous statistical control for multiple comparisons, only total IgE, absolute basophil count, and eosinophil percentage correlated significantly with symptom severity, highlighting their potential as accessible biomarkers for assessing disease activity.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 3","pages":"255-268"},"PeriodicalIF":1.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of core immuno-inflammatory mechanisms and key regulatory targets in psoriasis.","authors":"Wenli Zhou, Zhaoyu Li, Xuehai Liu, Binkui Jia, Xuedong Pei, Di Wang, Haoling Zhang, Sinong Wang","doi":"10.62347/YBMA7699","DOIUrl":"10.62347/YBMA7699","url":null,"abstract":"<p><p>Psoriasis is a chronic immune-mediated inflammatory skin disease caused by dysregulated interaction between innate and adaptive immune cells. Of note, the IL-23/Th17 axiom is new central circuit amongst known pathways, while TNF-alpha, IL-17 family cytokines and IL-36 mediate the dysfunction of keratinocyte and tissue in inflammation. An interconnecting inflammatory network involves dendritic cells, T-cell populations, keratinocytes, neutrophils and fibroblasts that plate epidermal hyperproliferation and lesional immune-cell recruitment. Biologics targeting TNF-alpha and IL-17 and IL-23 are clinically transformative in the treatment of disease, but a large cohort of patients are left with incomplete response, resistance or challenges in long-term management. Other novel targets such IL-36R and AHR may extend the window of therapeutic opportunity. Molecular stratification and biomarker-driven treatment selection also merit investigation in parallel with further delineation of a specific therapeutic strategy.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 3","pages":"156-192"},"PeriodicalIF":1.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148563966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-inflammatory macrophage-BMSC crosstalk enhances osteogenesis with attenuation of oxidative stress.","authors":"Tian Tian, Changhuan Liu, Lingnan Zhang, Ming Yu, Fang Wang, Wenling Wang, Jing Wang, Xiangrui Ma","doi":"10.62347/BWGO6836","DOIUrl":"10.62347/BWGO6836","url":null,"abstract":"<p><strong>Aim: </strong>Macrophage-mesenchymal stem cell (MSC) interactions critically influence bone regeneration during periodontitis resolution. While macrophage polarization under strong inflammatory conditions has been well studied, the functional role of macrophages exposed to low-grade inflammatory stimulation and their impact on MSC osteogenesis remain poorly understood.</p><p><strong>Methods: </strong>RAW264.7 macrophages were stimulated with reduced doses of classical M1 inducers to generate a low-inflammatory transitional phenotype (M1^semi). Macrophage polarization and inflammatory cytokine expression were assessed by quantitative real-time PCR. M1^semi macrophages were co-cultured with bone marrow mesenchymal stem cells (BMSCs) using conditioned medium, Transwell indirect co-culture, or direct cell-cell contact, with or without oxidative stress induction by hydrogen peroxide. Intracellular reactive oxygen species (ROS) levels in BMSCs were evaluated by fluorescence staining, and osteogenic differentiation was assessed by alkaline phosphatase (ALP) staining, ALP activity, and osteogenic gene expression.</p><p><strong>Results: </strong>Compared with classically activated M1 macrophages, M1^semi macrophages exhibited reduced expression of pro-inflammatory cytokines and a polarization profile intermediate between M1 and M2 phenotypes. Among the co-culture systems tested, only direct contact with M1^semi macrophages significantly enhanced osteogenic and angiogenic marker expression and increased ALP activity in BMSCs. This osteogenic enhancement was accompanied by a marked reduction in intracellular ROS levels. Importantly, exogenous induction of oxidative stress attenuated both ROS suppression and the osteogenic effects observed in direct co-culture.</p><p><strong>Conclusion: </strong>Macrophages exposed to low-grade inflammatory stimulation acquire a transitional phenotype with distinct immunomodulatory properties. Direct interaction with these macrophages enhances BMSC osteogenic differentiation, which is associated with reduced intracellular ROS accumulation. These findings suggest that modulation of oxidative stress contributes to macrophage-mediated osteogenesis in low-inflammatory environments, providing insight into immune-regulated bone regeneration during periodontal healing.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 2","pages":"99-111"},"PeriodicalIF":1.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventing sino-nasal polyposis recurrence after functional endoscopic sinus surgery: a multicentric study.","authors":"Goran L Omer","doi":"10.62347/KYDI9328","DOIUrl":"10.62347/KYDI9328","url":null,"abstract":"<p><strong>Background: </strong>Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently recurs after functional endoscopic sinus surgery (FESS), particularly in patients with eosinophilic inflammation or aspirin-exacerbated respiratory disease (AERD). Optimizing postoperative medical regimens based on disease severity may reduce recurrence rates. The aim of this study was to evaluate the impact of severity-based postoperative medical regimens on recurrence rates following FESS in patients with CRSwNP.</p><p><strong>Methods: </strong>This prospective multicentric cohort study included 144 patients with CRSwNP who underwent FESS between 2021 and 2023. Patients were stratified into five groups based on eosinophilia, AERD status, and radiologic/endoscopic severity using the Modified Lund-Mackay (MLM) and Modified Lund-Kennedy (MLK) scores. Each group received a tailored postoperative medical regimen. Patients were followed for two years, with recurrence assessed via nasal endoscopy and scored using MLK.</p><p><strong>Results: </strong>The overall recurrence rate at two years was 10.4%. Recurrence rates increased progressively from 0% in Group 1 (non-eosinophilic) to 33.3% in Group 5 (AERD). The trend was statistically significant (Cochran-Armitage test, Z = 3.48, P < 0.001). A significant association between follow-up group and recurrence was found (Chi-square, P = 0.006, Cramér's V = 0.316). Blood eosinophilia and elevated IgE levels were strongly correlated (P < 0.001, OR = 3.15).</p><p><strong>Conclusion: </strong>Postoperative recurrence in CRSwNP can be significantly reduced by tailoring medical regimens based on clinical, radiologic, and immunologic severity. Group-based stratification provides a feasible model for personalizing care, especially in settings where biologics are unavailable.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 2","pages":"124-132"},"PeriodicalIF":1.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared gene signatures between rheumatoid arthritis and Sjögren's syndrome.","authors":"Yi-Fan Li, Zhao-Wei Gao, Li Liu, Xi Wang, Kun Fan, Fang Lin, Ruo-Xuan Hei","doi":"10.62347/QHVD4331","DOIUrl":"10.62347/QHVD4331","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to multiple complications. Sjögren's syndrome (SS) is another autoimmune condition that may occur as a primary disorder or in conjunction with other autoimmune diseases, including RA. This study aimed to investigate the shared gene signatures between RA and SS. Gene expression datasets for RA (GSE15573, GSE93776) and SS (GSE48378, GSE94510, GSE93683) were obtained and analyzed to identify differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) and T cells. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the DEGs identified. Quantitative real-time PCR (qRT-PCR) was used to validate the expression levels of DEGs in PBMCs from patients with RA and SS. A total of 244 DEGs were identified from the RA PBMC dataset, comprising 142 upregulated genes and 102 downregulated genes. These DEGs were significantly enriched in biological processes related to immune responses, including cellular response to lipopolysaccharide, defense response against fungi, inflammatory responses, and antibacterial humoral responses. In contrast, 335 DEGs were identified from the SS PBMC dataset; among these, 320 genes were upregulated, while 15 were downregulated. The DEGs associated with SS showed strong involvement in defense responses against viruses, innate immune responses, viral responses, as well as cellular reactions to lipopolysaccharide. Moreover, we identified 12 shared DEGs between RA and SS PBMCs: RNASE2, NDUFB3, LY96, ANKRD22, EIF2AK2, RNASE3, CLEC4D, TNFAIP6, DYNLT1, RPS27L, LILRA5, and F5. Validation through qRT-PCR confirmed increased expression levels of RNASE2, RNASE3, NDUFB3, and EIF2AK2 in PBMCs. This study successfully delineated key DEGs along with their associated biological processes within the context of RA and SS PBMCs. Through bioinformatics analyses combined with qRT-PCR validation, we have identified four critical genes that may serve as potential biomarkers or therapeutic targets for further investigation.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 2","pages":"112-123"},"PeriodicalIF":1.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antagonists of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) as rationale and therapeutic potential of combination cancer therapy.","authors":"Hai Qian, Ying Wang, Kwaku Appiah-Kubi","doi":"10.62347/PSYP3847","DOIUrl":"10.62347/PSYP3847","url":null,"abstract":"<p><p>Platelet-Derived Growth Factor (PDGF)/Platelet-Derived Growth Factor Receptor (PDGFR) are key regulators in the complex network of signaling from Receptor Tyrosine Kinases (RTKs). PDGFR has historically been considered an attractive therapeutic target given its association with oncogenic mutations, gene fusions and altered signaling. However, growing evidence suggests that PDGFR functions beyond these traditional roles as a single therapeutic target and into a broader role as a central coordinator of oncogenic signaling. PDGFR mediates cross-talk among multiple oncogenic pathways such as EGFR, VEGFR and IGF-1R thus supporting redundancy in oncogenic signaling, resistance to therapy and adaptive changes in tumors. The biologic effects of PDGFR signaling do not end at tumor cell borders but rather include the regulation of the tumor microenvironment. Specifically, PDGFR directs the recruitment of pericytes, remodeling of the extracellular matrix and influences interstitial fluid pressure (IFP); each effect ultimately impacts both drug delivery and therapeutic efficacy. Studies have demonstrated that inhibition of PDGFR reduces stromal tension and normalizes tumor vasculature resulting in enhanced penetration of chemotherapy, targeted and radiation therapy. As such, these studies provide rationale for using PDGFR directed strategies in order to enhance treatment outcome via rational combinations of drugs. This review aims to integrate current knowledge of PDGF/PDGFR biology based on molecular interactions, tumor microenvironment dynamics and therapeutic approaches. It will highlight how PDGFR directed therapeutic strategies may serve to circumvent drug resistance, enhance drug delivery, enable use of biomarkers to drive combination therapeutics and promote a systems-level understanding of PDGFR function as a basis for advancing its translational application in precision oncology.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 2","pages":"148-155"},"PeriodicalIF":1.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic exercise versus acupuncture as adjuncts to acetylcholinesterase inhibitors in Alzheimer's disease: a systematic review and Bayesian network meta-analysis.","authors":"Zhaoxie Yu, Hanzhang Li, Yao Wang, Feng Shen, Yanchun Wang","doi":"10.62347/FDDF9443","DOIUrl":"10.62347/FDDF9443","url":null,"abstract":"<p><strong>Background: </strong>Acetylcholinesterase inhibitors (AChEIs) remain the standard therapy for Alzheimer's disease (AD), yet their cognitive and functional benefits are limited, creating a strong need for effective adjunctive treatments. Aerobic exercise and acupuncture have been proposed as promising complements to AChEIs because of their potentially synergistic neurotrophic and cholinergic effects. To compare these treatment combinations, we carried out a Bayesian network meta-analysis (BNMA) of randomized controlled trials (RCTs). These studies were sourced from major English and Chinese databases and examined cognitive and functional outcomes. In total, 37 RCTs were included, covering 2,188 participants. Among all, combined acupuncture (SUCRA = 78.92%) and fire needle therapy (SUCRA = 78%) demonstrated the highest probability of improving Mini Mental State Examination scores, while moderate intensity aerobic exercise ranked best for the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog, SUCRA = 23.3%) and the Barthel Index (SUCRA = 71.1%). Combined acupuncture was ranked highest for the Alzheimer's Disease Assessment Scale-Activities of Daily Living (ADAS-ADL, SUCRA = 94.3%), although its effects did not reach statistical significance. Across analyses, heterogeneity was minimal (I² ≤ 4%), model convergence was stable, and no publication bias was detected. Overall, this BNMA suggests that combined or thermal acupuncture offers the strongest cognitive gains alongside AChEIs, whereas moderate-intensity aerobic exercise provides the most reliable functional support. Because overall functional improvements were modest and evidence for some interventions remains limited, the benefits appear selective rather than broad. Larger, standardized trials are needed to clarify these patterns and guide their use in practice.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 2","pages":"37-49"},"PeriodicalIF":1.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-21 expression during sublingual immunotherapy for allergic rhinitis.","authors":"Chunrui Wang, Xiaowei Qin, Li Jiang, Tianhong Zhang","doi":"10.62347/XBRN4628","DOIUrl":"10.62347/XBRN4628","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis (AR) is an inflammatory disorder involving immunoglobulin E (IgE)-mediated immune response. Interleukin (IL)-21 IL-21 can regulate immune cell functions and IgE production. We aimed to explore the modulation of IL-21 expression before and after sublingual immunotherapy (SLIT) in AR patients and its correlation with IgE and Th2 cytokines.</p><p><strong>Methods: </strong>Fifty AR patients were enrolled and treated with HDM allergen extract via SLIT. Serum levels of IL-21 and Th2 cytokines as well as IgE were determined using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed to compare changes in cytokine levels and assess correlations.</p><p><strong>Results: </strong>After 3 years of SLIT, serum levels of IL-21, Th2 cytokines and IgE were significantly reduced. Greater decreases were found in the effective treatment group compared to the ineffective group. The expression of IL-21 was correlated to IL-4 and IgE levels.</p><p><strong>Conclusion: </strong>SLIT downregulates the expression of IL-21 and other Th2 cytokines, with IL-21 potentially serving as a biomarker for SLIT efficacy in AR patients.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 2","pages":"142-147"},"PeriodicalIF":1.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-metabolic crosstalk in rheumatoid arthritis: mediation effects of plasma metabolites on inflammatory cytokines.","authors":"Yuting Liang, Yanqiu Zhang, Jieyu Jin, Bin Feng, Jun Qiu, Jun Cao","doi":"10.62347/PLPF4012","DOIUrl":"10.62347/PLPF4012","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rheumatoid arthritis (RA) is a chronic inflammatory condition defined by synovitis and progressive joint damage. The connection between inflammatory cytokines, molecules, and RA is still poorly understood despite the information combining both immune dysregulation and metabolic reprogramming to its pathophysiology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A two-sample Mendelian randomization (MR) analysis was carried out using summary statistics from the largest-scale genome-wide association study (GWAS) to examine the link between 91 inflammatory cytokines and RA risk. Metabolite pathways were identified through mediation analysis. Multiple MR Methods including inverse variance weighting (IVW) were used for causal estimation and the hypothesis was verified by sensitivity analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The analysis results showed that there was a causal association between six inflammatory cytokines and RA. Among them, HGF and IL-10RA increased the risk of RA, while CXCL9, EN-RAGE, IFN-γ and CCL8 showed protective effects. These associations were validated using multiple MR methodologies, including inverse-variance weighting, MR-Egger regression, and leave-one-out sensitivity analyses. Further mediation MR analysis revealed seven metabolite-mediated pathways of inflammatory cytokines and RA. Specifically, the protective effect of CXCL9 was achieved in part by reducing plasma eicosapentaenoic acid (EPA; 20:5n3) levels (mediating effect = -0.007; proportion mediated = 8.10%). The protective effect of EN-RAGE was mediated by a decrease in the level of salicyluric glucuronide (mediating effect = -0.015; 12.70%). IFN-γ reduced the risk of RA through two independent metabolic pathways: reducing the level of 1-arachidonoyl-glycerol-3-phosphocholine (20:4n6) levels (mediating effect = -0.005; 4.67%), and increasing the ratio of glycine-to-pyridoxal (mediating effect = -0.020; 19.60%). In contrast, IL-10RA increases the risk of RA by increasing 3,7-dimethylurate (mediating effect = 0.011; 12.50%) and decreasing N, N-dimethylalanine levels (mediating effect = 0.010; 11.70%). The protective effect of CCL8 was mediated by the reduction of specific sphingomyelin species (d17:2/16:0, d18:2/15:0) (mediating effect = -0.012; 12.30%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The results of this study not only confirmed the causal role of specific inflammatory cytokines in the pathogenesis of RA from a genetic perspective, but more importantly, for the first time, systematically revealed the specific plasma metabolite mediating pathways that connect these inflammatory cytokines to RA. These findings more specifically link the immune dysregulation of RA to metabolic remodeling, especially the protective role of IFN-γ through glycine/pyridoxal balance, and the pathway of IL-10RA through purine metabolites to affect risk, providing novel and mechanistic insights into the immunometabolic network of RA. We believe that these specific interm","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 2","pages":"87-98"},"PeriodicalIF":1.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrospective analysis of von willebrand factor and microthrombus formation in septic shock: associations with TTP-like syndrome and sepsis-induced coagulopathy.","authors":"Yi Liu, Jinxi Yue, Qingqing Huang, Linjun Wan, Weili Zhao, Zongfang Ren, Chen Han, Bangting Zhang, Changjiang Li, Li Pan, Haoling Zhang, Jingjing Zhang","doi":"10.62347/MVAS2552","DOIUrl":"10.62347/MVAS2552","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis shock is characterized by endothelial damage and coagulation abnormalities. However, the relationship between von Willebrand factor (vWF), microthrombosis, and various clinical phenotypes such as thrombotic thrombocytopenic purpura (TTP) and sepsis-induced coagulopathy (SIC) has not been fully elucidated.</p><p><strong>Methods: </strong>This retrospective study enrolled 147 patients with septic shock admitted to the ICU in 2023, all of whom underwent vWF antigen testing. The patients were divided into three groups: the TTP-like group, the SIC group, and the control group. Platelet (PLT) indices, vWF levels, SOFA subscores, incidence of organ dysfunction, and 28-day mortality were compared. Correlation analyses and non-parametric tests were performed.</p><p><strong>Results: </strong>The SIC group showed significantly lower nadir PLT counts and higher PLT decline rates compared with the TTP-like and control groups (P < 0.05). vWF levels were elevated across all groups and were significantly higher in the TTP-like and SIC groups versus controls (P < 0.05). vWF levels correlated negatively with nadir PLT (r = -0.20, P = 0.018). Both TTP-like syndrome and SIC were associated with high rates of MODS; however, hepatic and renal injury, number of dysfunctional organs, and 28-day mortality were significantly worse in the SIC group (P < 0.05).</p><p><strong>Conclusion: </strong>Elevated vWF is associated with diffuse microthrombus formation in septic shock and may serve as a marker of endothelial injury. While both TTP-like syndrome and SIC contribute to organ dysfunction, SIC is associated with more severe organ injury and higher mortality. Prospective studies are needed to validate these findings.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":"15 2","pages":"133-141"},"PeriodicalIF":1.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}