Piao Guo, Xue Ning Zhang, Xin Yu Jin, Wen Juan Xia, Li Zhou, Wei Song Sheng, Dan Rong Zhu
{"title":"Clinical Efficacy of Transcutaneous Electrical Nerve Stimulation (TENS) in Pediatric Functional Constipation: Impact on Immunological Indicators and Gut Microbiota.","authors":"Piao Guo, Xue Ning Zhang, Xin Yu Jin, Wen Juan Xia, Li Zhou, Wei Song Sheng, Dan Rong Zhu","doi":"10.1155/jimr/8888730","DOIUrl":"https://doi.org/10.1155/jimr/8888730","url":null,"abstract":"<p><p><b>Objective:</b> This study was conducted to evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) in treating pediatric functional constipation (FC) and to explore its mechanisms by analyzing changes in serum neurotransmitters and gut microbiota. <b>Materials and Methods:</b> This was a prospective cohort study conducted on 60 children aged 4-14 years diagnosed with FC. Participants were divided into two groups, namely, one receiving TENS therapy three times a week for 4 weeks and the control group receiving lactulose. Pretreatment and posttreatment evaluations included serum neurotransmitters, immunological indicators, and gut microbiota composition. <b>Results:</b> The TENS group demonstrated significant improvements in defecation frequency and constipation symptoms compared with the lactulose group (<i>p</i> < 0.001). Posttreatment, remarkable increases were detected in serum motilin and vasoactive intestinal peptide (VIP) levels, along with a significant decrease in interleukin-12 levels (<i>p</i> < 0.05), indicating anti-inflammatory effects. Gut microbiota analysis revealed significant shifts in microbial composition, with an increase in the abundance of Bacteroidetes and a decrease in the abundance of Firmicutes/Bacteroidetes ratio, suggesting improved gut health and metabolic function. <b>Conclusion:</b> TENS effectively improves symptoms of pediatric FC and induces beneficial changes in immunological indicators and gut microbiota. These results suggest potential anti-inflammatory and microbiota-modulating effects. However, due to the limited sample size, further studies are needed to confirm these findings and explore the long-term benefits of TENS therapy. <b>Trial Registration:</b> Clinical Trial Registry identifier: ChiCTR2200059549.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"8888730"},"PeriodicalIF":3.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Global Trends in Research of Amino Acid Metabolism in T Lymphocytes in Recent 15 Years: A Bibliometric Analysis.","authors":"Jiaona Xu, Yinan Yu, Shijie Li, Fanghui Qiu","doi":"10.1155/jimr/3393342","DOIUrl":"10.1155/jimr/3393342","url":null,"abstract":"<p><p>Amino acid metabolism in T cells determines the therapeutic efficacy of T-cell-targeting drugs. To assess the direction of amino acid metabolism in T cells and construct related knowledge structure, we performed a bibliometric analysis aiming at amino acid metabolism in T cells utilizing studies publicized in recent 15 years. Three hundred thirty-seven related studies were downloaded from the Web of Science Core Collection (WoSCC), and the information on countries, institutes, and authors was collected and analyzed. In addition, the present research status and future trends were explored according to the results yielded from the analysis of cited references and keywords. This study revealed that publications regarding amino acid metabolism in T cells gradually increased each year. The USA is the top producer and most influential country in this field. Recent research has focused on the correlation between the metabolism of several amino acids and regulatory T cells (Tregs) and CD8<sup>+</sup> T cells. Overall, this research offers a comprehensive exhibition on the field of amino acid metabolism in T cells, which will help researchers to study this domain more effectively and intuitively.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"3393342"},"PeriodicalIF":3.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11824865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancements and Future Directions of Dual-Target Chimeric Antigen Receptor T-Cell Therapy in Preclinical and Clinical Studies.","authors":"Chenyun Zhang, Haizhou Liu","doi":"10.1155/jimr/5845167","DOIUrl":"10.1155/jimr/5845167","url":null,"abstract":"<p><p>In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made groundbreaking progress in the treatment of various cancer types, particularly hematological malignancies. In the meantime, various preclinical and clinical studies have extensively explored dual-target CAR-T therapies which can be designed to recognize two antigens simultaneously based on the immunophenotype of tumor cells. Compared with single-target CAR-T approach, dual-target CAR-T therapies demonstrate varying degrees of superior antitumor CAR effects, prevent antigen escape and relapse, reduce on-target off-tumor effects, and ensure durable responses in different types of cancer. These advantages highlight the potential future prospects in this field, showing varying degrees of advancement in preclinical and clinical studies. Herein, we aimed to review different dual-target CAR-T studies conducted on a wide range of tumor models, summarizing the selection of target combinations, the efficacy and safety demonstrated in preclinical and clinical settings, the existing limitations, and the potential future directions of this promising therapeutic strategy.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"5845167"},"PeriodicalIF":3.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NF-<i>κ</i>B Inhibitory Activity of the Di-Hydroxy Derivative of Piperlongumine (PL-18).","authors":"Yael Schlichter Kadosh, Subramani Muthuraman, Ariel Kushmaro, Rajendran Saravana Kumar, Jacob Gopas","doi":"10.1155/jimr/9915695","DOIUrl":"https://doi.org/10.1155/jimr/9915695","url":null,"abstract":"<p><p>Inflammation is a critical response of the immune system to infection or injury, serving to repair and restore tissue homeostasis. While acute inflammation generally protects against harmful stimuli, prolonged and chronic inflammation have detrimental effects and disrupts tissue homeostasis. Due to the complex and multifactorial etiology of chronic inflammation, effective treatment remains elusive. We found that piperlongumine (PL)-18, a di-hydroxy derivative of PL from long pepper, inhibits the nuclear factor kappa B (NF-<i>k</i>B), a master transcription factor of numerous components of the inflammatory response. NF-<i>k</i>B was inhibited by PL-18 in two human cell-lines, L428 and A549, by preventing the nuclear translocation of p65 NF-<i>k</i>B. We also found that I<i>κ</i>B kinase (IKK) was degraded in the presence of PL-18. Furthermore, PL-18 inhibited the production of proinflammatory cytokines expressed by L428, a cell line with a constitutive active NF-<i>k</i>B. Altogether, our results suggest that PL-18 is a molecule of interest to be further developed to treat persistent infections with severe inflammation.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"9915695"},"PeriodicalIF":3.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lei Han, Tianxiang Wu, Qin Zhang, Anning Qi, Xiaohui Zhou
{"title":"Immune Tolerance Regulation Is Critical to Immune Homeostasis.","authors":"Lei Han, Tianxiang Wu, Qin Zhang, Anning Qi, Xiaohui Zhou","doi":"10.1155/jimr/5006201","DOIUrl":"10.1155/jimr/5006201","url":null,"abstract":"<p><p>The body's immune response plays a critical role in defending against external or foreign antigens while also preserving tolerance to self-antigens. This equilibrium, referred to as immune homeostasis, is paramount for overall health. The regulatory mechanisms governing the maintenance of this delicate immune balance are notably complex. It is currently accepted that immune tolerance is a dynamic outcome regulated by multiple factors, including central and peripheral mechanisms. Its induction or elimination plays a significant role in autoimmune diseases, organ transplantation, and cancer therapy, markedly impacting various major diseases in modern clinical practice. Overall, our current understanding of immune tolerance is still very limited. In this review article, we summarized the main mechanisms that have been known to mediate immune tolerance so far, including endogenous immune tolerance, adaptive immune tolerance, other immune tolerance mechanisms, and the homeostasis of immune tolerance, identified the key factors that regulate immune tolerance, and provided new clues for immune system recovery in many autoimmune diseases, organ transplantation, and tumor therapy.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"5006201"},"PeriodicalIF":3.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11824399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Roles of NET Peptides With Known Antimicrobial Activity and Toxicity in Immune Response.","authors":"Sinan Cebeci, Tuba Polat, Nihan Ünübol","doi":"10.1155/jimr/5528446","DOIUrl":"https://doi.org/10.1155/jimr/5528446","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) are crucial components of the innate immune system in all living organisms, playing a vital role in the body's defense against diseases and infections. The immune system's primary functions include preventing disease-causing agents from entering the body and eliminating them without causing harm. These peptides exhibit broad-spectrum activity against bacteria, viruses, fungi, parasites, and cancer cells. They are secreted by innate and epithelial cells and contribute to host defense by inducing cellular activities such as cell migration, proliferation, differentiation, cytokine production, angiogenesis, and wound healing. In response to the growing challenge of bacterial resistance to antimicrobial agents, alternative drugs and new antibacterial molecules are being explored. In a previous study, NET AMPs were synthesized and their antimicrobial effects were determined. The current study extends this work by assessing the effects of these peptides on the immune system through cell culture experiments and ELISA. Specifically, the study investigated how different concentrations of these peptides influence the secretion of interleukin-6 (IL-6), tumor necrosis factor-<i>α</i> (TNF-<i>α</i>), and interferon-<i>γ</i> (IFN-<i>γ</i>) in mouse macrophages. Among the synthesized peptides, NET1 and NET2 demonstrated low cytotoxicity in TIB-71 RAW 264.7 macrophages. These peptides induced an anti-inflammatory response and reduced IL-6 expression in the absence of LPS stimulation, while simultaneously increasing IFN-<i>γ</i> and TNF-<i>α</i> secretion. These findings suggest that NET1 and NET2 peptides possess both anti-inflammatory and pro-inflammatory properties, highlighting their potential role in modulating immune responses.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"5528446"},"PeriodicalIF":3.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic Reprograming of Macrophages: A New Direction in Traditional Chinese Medicine for Treating Liver Failure.","authors":"Junli Zhang, Na Li, Xiaoyu Hu","doi":"10.1155/jimr/5891381","DOIUrl":"10.1155/jimr/5891381","url":null,"abstract":"<p><p>Acute liver failure (ALF) is a fulminant clinical syndrome that usually leads to multiple organ failure and high mortality. Macrophages play a crucial role in the initiation, development, and recovery of ALF. Targeting macrophages through immunotherapy holds significant promise as a therapeutic strategy. These cells exhibit remarkable plasticity, enabling them to differentiate into various subtypes based on changes in their surrounding microenvironment. M1-type macrophages are associated with a pro-inflammatory phenotype and primarily rely predominantly on glycolysis. In contrast, M2-type macrophages, which are characterized by anti-inflammatory phenotype, predominantly obtain their energy from oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). Shifting macrophage metabolism from glycolysis to OXPHOS inhibits M1 macrophage activation and promotes M2 macrophage activation, thereby exerting anti-inflammatory and reparative effects. This study elucidates the relationship between macrophage activation and glucose metabolism reprograming from an immunometabolism perspective. A comprehensive literature review revealed that several signaling pathways may regulate macrophage polarization through energy metabolism, including phosphatidyl-inositol 3-kinase/protein kinase B (PI3K/AKT), mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1<i>α</i> (HIF-1<i>α</i>), nuclear factor-<i>κ</i>B (NF-<i>κ</i>B), and AMP-activated protein kinase (AMPK), which exhibit crosstalk with one another. Additionally, we systematically reviewed several traditional Chinese medicine (TCM) monomers that can modulate glucose metabolism reprograming and influence the polarization states of M1 and M2 macrophages. This review aimed to provide valuable insights that could contribute to the development of new therapies or drugs for ALF.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"5891381"},"PeriodicalIF":3.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongwen Liu, Shiguo Yuan, Kai Zheng, Gaofeng Liu, Junhua Li, Baofei Ye, Yangkun Wang, Li Yin, Yikai Li
{"title":"Manual Therapy Exerts Local Anti-Inflammatory Effects Through Neutrophil Clearance.","authors":"Hongwen Liu, Shiguo Yuan, Kai Zheng, Gaofeng Liu, Junhua Li, Baofei Ye, Yangkun Wang, Li Yin, Yikai Li","doi":"10.1155/2024/5556042","DOIUrl":"https://doi.org/10.1155/2024/5556042","url":null,"abstract":"<p><p><b>Background:</b> Manual therapy (MT) has been widely used in China to treat local tissue inflammation for a long time. However, there is a lack of scientific evidence for using MT in anti-inflammatory therapy, and its anti-inflammatory mechanism needs further clarification. <b>Methods:</b> We utilized MT to treat cardiotoxin (CTX) injury-induced skeletal muscle inflammation in C57BL6/J mice. We analyzed the underlying mechanism by integrating single-cell RNA sequencing (scRNA-seq) with molecular techniques. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were used to assess skeletal muscle inflammation and muscle fiber cross-sectional area (CSA). scRNA-seq, immunofluorescence, and western blot were performed to determine cellular and molecular outcome changes. <b>Results:</b> Compared with CTX injury-induced skeletal muscle inflammatory mice, MT intervention significantly reduced proinflammatory cytokines interleukin (IL)-1<i>β</i>, IL-6, and tumor necrosis factor alpha (TNF-<i>α</i>) expression levels; scRNA-seq detected that neutrophil numbers and activity were maximum proportions increased in injured skeletal muscle among macrophage, T cells, B cells, endothelial cells, fast muscle cells, fibroblasts, and skeletal muscle satellite cells; and S100A9 gene expression was supreme in neutrophils. However, after treatment with MT, S100A9 protein expression and the numbers and activity of Ly6g+/Mpo+ neutrophils were significantly inhibited, thus reducing the inflammatory cytokine levels and exerting an anti-inflammatory effect by early clearing neutrophils. <b>Conclusion:</b> MT can mitigate localized inflammation induced by injured skeletal muscle, achieved by decreasing S100A9 protein expression and clearing neutrophils in mice, which may help advance therapeutic strategies for skeletal muscle localized inflammation.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"5556042"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Construction of the miRNA/Pyroptosis-Related Molecular Regulatory Axis in Abdominal Aortic Aneurysm: Evidence From Transcriptome Data Combined With Multiple Machine Learning Approaches Followed by Experiment Validation.","authors":"Yongchao Su, Chuangang Lu, Shuchen Chen","doi":"10.1155/2024/1429510","DOIUrl":"https://doi.org/10.1155/2024/1429510","url":null,"abstract":"<p><p><b>Background:</b> Abdominal aortic aneurysm (AAA) represents a permanent and localized widening of the abdominal aorta, posing a potentially lethal risk of aortic rupture. Several recent studies have highlighted the role of pyroptosis, a pro-inflammatory programed cell death, as critical molecular regulators in AAA occurrence, progression, and rupture. However, the potential effects of pyroptosis in AAA and its upstream microRNA (miRNA) have not been comprehensively clarified. <b>Methods:</b> Through a search of the gene expression omnibus (GEO) database, the expression profiles of mRNAs (GSE7084, GSE57691, and GSE98278) and miRNAs (GSE62179) and corresponding clinical features were downloaded, respectively. Expression profiles of 15 AAA and 10 normal vascular samples were consecutively collected for in vitro experimentation and subsequent analysis. Various machine learning techniques were employed to identify hub pyroptosis-related genes (PRGs), leading to the development of a predictive model termed the PRG classifier. Quantitative real-time-polymerase chain reaction (qRT-PCR), western blot (WB), and enzyme-linked immunosorbent assay (ELISA) were used to confirm the expression of the hub PRGs. The diagnostic and predictive capabilities of the model were comprehensively evaluated in GEO and hospital cohorts. Then, the crucial immune cell infiltration and molecular pathways implicated in the initiation and rupture of AAA and their association with pyroptosis were explored. Lastly, a miRNA/hub pyroptosis-related molecular regulatory axis was constructed using the TargetScan dataset, which was further explored through loss-of-function assays. <b>Results:</b> Differential analysis, enrichment score analysis, and principal component analysis (PCA) revealed that pyroptosis-related molecules were significantly involved in the occurrence of AAA. Utilizing multiple machine learning algorithms, eight key PRGs (cysteinyl aspartate specific proteinase [CASP]1, infiltrating lymphocyte [IL]1B, IL18, IL6, NOD-, LRR- and pyrin domain-containing protein [NLRP]1, NLRP2, NLRP3, and tumor necrosis factor [TNF]) were integrated to establish a PRG classifier. Demonstrating robust diagnostic capabilities (area under curve [AUC] > 0.90), the PRG classifier provided clinical insights across two GEO datasets and effectively differentiated small AAA from large AAA, elective stable AAA (eAAA), and ruptured AAA (rAAA), respectively. qRT-PCR, WB, and ELISA verified the mRNA and protein expression of the hub PRGs. Notably, in hospital cohorts, a substantial positive link was unveiled between the PRG classifier and AAA risk factors (hypertension history, diastolic pressure, triglyceride levels, and aneurysm diameter). Furthermore, immune cell infiltration and functional enrichment analysis revealed significant associations of the PRG classifier/PRGs with M2 macrophage infiltration, activated dendritic cells, and enrichment scores of the cytosolic deoxyribonucleic acid (","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"1429510"},"PeriodicalIF":3.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weiyong Zhong, Chaoting Lan, Yuqiong Chen, Kai Song, Zuyi Ma, Jixiao Zeng, Lihua Huang, Yan Zhang, Yun Zhu, Huimin Xia
{"title":"Virus-Triggered Autoimmunity Was Associated With Hirschsprung's Disease Through Activation of Innate Immunity.","authors":"Weiyong Zhong, Chaoting Lan, Yuqiong Chen, Kai Song, Zuyi Ma, Jixiao Zeng, Lihua Huang, Yan Zhang, Yun Zhu, Huimin Xia","doi":"10.1155/2024/4838514","DOIUrl":"10.1155/2024/4838514","url":null,"abstract":"<p><p><b>Background:</b> Hirschsprung's disease (HSCR) is a congenital enteric nervous system (ENS) disorder. Genetics cannot explain most sporadic cases. To explore the relationship between pathogen infection, autoantibodies, innate immune, and HSCR. <b>Methods:</b> Pathogen microarray was conducted in the serum of the prospective neonatal abdominal distension (NAD) cohort, consisting of 56 children followed for at least 6 months until the final diagnosis of HSCR was determined or excluded. We conducted an autoantibody microarray in an HSCR cohort, which is comprised of diagnosed HSCR patients (HSCR) and healthy control subjects (HC). RNA-seq of colon tissues from aganglionic and ganglionic segments of HSCR patients was performed. <b>Results:</b> Experimental results show that the serum lgM and lgG of enterovirus 71 (EV71) were significantly higher in HSCR than in the gastrointestinal dysfunction (GI) group, with a prediagnose value reaching area under the curve (AUC) over 0.76. We discovered that a group of autoantibodies were significantly higher in HSCR including neuronal pentraxin 1 (NPTX1), amyloid, neuron lysate, and myelin-associated oligodendrocytic basic protein (MOBP) than that in the HC group. These four autoantibodies could distinguish HSCR from the HC group, with a combined AUC of over 0.90 using both serum IgG and IgM. Further analysis showed that wide activation of innate immune pathways, including toll-like receptor (TLR) signaling pathway, neutrophil-to-lymphocyte ratio (NLR) signaling pathway, red cell distribution width to lymphocyte ratio (RLR) signaling pathway, and cyclic adenosine monophosphate (cAMP) signaling pathway in aganglionic compared to ganglionic segments of HSCR. <b>Conclusion:</b> This study suggested that virus-triggered autoimmunity may contribute to HSCR through activation of innate immunity, which facilitates the diagnosis and prevention of HSCR.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2024 ","pages":"4838514"},"PeriodicalIF":3.5,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}