Innate Immunity最新文献

{"title":"Preclinical development of the TLR4 antagonist FP12 as a drug lead targeting the HMGB1/MD-2/TLR4 axis in lethal influenza infection.","authors":"Kari Ann Shirey, Alessio Romerio, Mohammed Monsoor Shaik, David S Leake, Charys Palmer, Natalia Skupinska, Jules Paton, Grisha Pirianov, Jorge Cg Blanco, Stefanie N Vogel, Francesco Peri","doi":"10.1177/17534259241313201","DOIUrl":"10.1177/17534259241313201","url":null,"abstract":"<p><strong>Background: </strong>Acute Lung Injuries (ALI) are a severe consequence of influenza-induced cytokine storm that can cause respiratory failure and death. It has been demonstrated that Toll-like Receptor 4 (TLR4) is involved in cytokine storm and that TLR4^-/- mice are protected against ALI. Therefore, TLR4 is a prime target for protection against ALI. FP12 is a known TLR4 antagonist that reduces TLR4-dependent immune activation and it is a promising lead compound for the treatment of innate immunity related pathologies.</p><p><strong>Objectives: </strong>We present here the preclinical development of FP12 as an anti-inflammatory lead compound acting on influenza-induced ALI.</p><p><strong>Methods: </strong><i>In vitro:</i> We pre-treated THP-1 cells with FP12 (10 μM) for 0.5 h, then exposed to LPS (100 ng/ml) for 0 to 16 h. In some experiments, cells were simultaneously incubated with FP12 and LPS, or FP12 was added 30 min after LPS. Cytokine levels were measured by Western blot and ELISA assays. <i>In vivo:</i> WT C57BL/6J mice were infected with mouse-adapted influenza virus (PR8). Two days after infection, mice received either vehicle, FP7 (200 µg/mouse), or FP12 (200 µg/mouse) once daily (Day 2 to Day 6). Mice were monitored daily for survival for 14 days. Data were collected through histological staining, qRT-PCR, and ELISA assay.</p><p><strong>Results: </strong>FP12 treatment inhibited both LPS- and HMGB1-induced TLR4 intracellular pathways (MyD88 and TRIF) leading to significantly reduced levels of a variety of proinflammatory cytokines including Type I interferon (IFN-β), highlighting its effectiveness in controlling proinflammatory protein production and reducing inflammation. FP12 protected mice therapeutically from influenza virus-induced lethality and reduced both cytokine gene expression and High Mobility Group Box 1 (HMGB1) levels in the lungs as well as ALI.</p><p><strong>Conclusion: </strong>FP12 can antagonize TLR4 activation in vitro and protects mice from severe influenza infection, most likely by reducing the TLR4-dependent cytokine storm mediated by danger-associated molecular patterns (DAMPs).</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259241313201"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking mucosal innate immune responses to three influenza A virus strains in a highly translational pig model using nasopharyngeal swabs.","authors":"Helena A Laybourn, Charlotte Kristensen, Anders G Pedersen, Louise Brogaard, Sophie George, Betina L Henriksen, Chrysillis H Polhaus, Ramona Trebbien, Lars E Larsen, Kerstin Skovgaard","doi":"10.1177/17534259251331385","DOIUrl":"10.1177/17534259251331385","url":null,"abstract":"<p><p>BackgroundFour influenza pandemics have occurred during the past 100 years, and new variants of influenza viruses will continue to emerge. The nasal mucosa acts as the primary site of exposure to influenza A virus (IAV) infection, but viral recognition and host immune responses in the nasal mucosa are still poorly understood.ObjectivesThis study aimed to evaluate the utility of non-invasive nasopharyngeal swabs for longitudinal monitoring of mucosal immune responses in pigs experimentally challenged with two swine-adapted and one human-adapted IAV. By tracking antiviral immune responses from disease onset to recovery, we sought to assess the feasibility of this method for capturing dynamic changes in viral load and host responses across different IAV strains.MethodsForty-two IAV-negative pigs were divided into four groups and housed separately for infection studies. Viral and host RNA from nasopharyngeal swabs was analyzed using microfluidic qPCR, while statistical analysis was performed with a Bayesian approach in R. Additionally, immunohistochemical staining was used to assess MUC5AC expression in the nasal mucosa of infected pigs.ResultsRNA was successfully isolated from nasopharyngeal swabs, enabling gene expression analysis to monitor innate immune responses to IAV infection. A classical innate antiviral immune response was demonstrated after the three virus infections including expression of pattern recognition receptors (PRRs), transcription factors, interferons (IFNs), interferon-stimulated genes (ISGs), cytokines, and chemokines. The kinetics and magnitude of immune responses varied between infections, with notable downregulation of mucins following infection with the Danish swine-adapted isolate. Further, the Danish isolate induced a fast but transient IFN-mediated response concurrent with high expression of cytokines and chemokines, while the other swine-adapted Mexican isolate induced a prolonged immune response of ISGs, cytokines, and chemokines.ConclusionThis study highlights the significance of highly translational nasopharyngeal swabs as a non-invasive method for assessing mucosal antiviral immune responses. Utilizing microfluidic mRNA analysis, we gained valuable insights into antiviral mucosal responses across 216 swab samples collected from viral inoculation through recovery in three distinct influenza virus infections.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251331385"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherent immunity and adaptive immunity: Mechanism and role in AECOPD.","authors":"Linguangjin Wu, Erxin Zhang, Yadan Tu, Yong Chen, Chenghu Wang, Yi Ren, Bangjiang Fang","doi":"10.1177/17534259251322612","DOIUrl":"10.1177/17534259251322612","url":null,"abstract":"<p><p>Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading cause of hospitalization and mortality in COPD patients. The occurrence of antibiotic resistance and the progression of non-infectious diseases contribute to poor patient outcomes. Thus, a comprehensive understanding of the mechanisms underlying AECOPD is essential for effective prevention. It is widely acknowledged that the immune system plays a fundamental role in pathogen clearance and the development of inflammation. Immune dysregulation, either due to deficiency or hyperactivity, has been implicated in AECOPD pathogenesis. Therefore, the purpose of this review is to investigate the possible mechanisms underlying dysregulated immune function and disease progression in COPD patients, specifically focusing on the innate and adaptive immune responses. The ultimate aim is to provide new insights for clinical prevention and treatment strategies targeting AECOPD.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251322612"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Rheumatic potential of biological DMARDS and protagonistic role of bio-markers in early detection and management of rheumatoid arthritis.","authors":"Muhammad Riaz, Ghulam Rasool, Ruhamah Yousaf, Hina Fatima, Naveed Munir, Hasan Ejaz","doi":"10.1177/17534259251324820","DOIUrl":"10.1177/17534259251324820","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects the synovial joint linings, resulting in progressive disability, increased mortality, and considerable economic costs. Early treatment with disease-modifying antirheumatic medications (DMARDs) can significantly improve the overall outlook for people with RA. Contemporary pharmaceutical interventions, encompassing standard, biological, and emerging small molecule disease- modifying anti-rheumatic medications continue to be the cornerstone of RA management, with substantial advancements made in the pursuit of achieving remission from the disease and preventing joint deformities. Nevertheless, a substantial segment of individuals with RA do not experience a satisfactory response to existing treatments, underscoring the pressing need for novel therapeutic options. Biologic DMARDs are among the therapy choices. Non-tumor necrosis factor inhibitors (Non-TNFi) such as abatacept, rituximab, tocilizumab, and sarilumab are examples, as are anti-tumor necrosis factor (TNF) medications such as infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol. More recent biomarkers have emerged and showed usefulness in the early detection of RA. These biomarkers, often referred to simply as \"biomarkers\", are quantifiable indicators of normal or pathologic processes, and they can also gauge treatment response. The assessment of RA treatment response typically combines patient-reported outcomes, physical evaluations, and laboratory findings, as there isn't a single biomarker that has proven sufficient for measuring disease activity. This review explores the usage of biologic DMARDs as a therapeutic approach for RA, as well as the biomarkers typically used for RA early diagnosis, prognosis prediction, and disease activity evaluation.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251324820"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The imbalance of circulating PD-L1-expressing non-classical/ classical monocytes is involved in immunocompromised host related pulmonary opportunistic infection.","authors":"Danhong Zhou, Yujia Jin, Yifan Jin, Yu Shen, Qiuxia Qu, Cheng Chen","doi":"10.1177/17534259251316152","DOIUrl":"10.1177/17534259251316152","url":null,"abstract":"<p><p>The application of biological therapy and glucocorticoids in Auto-immune diseases (AID) patients will cause immunocompromised host (ICH) prone to infection. And monocytes play a key role in both innate and adaptive immune responses. We aimed to investigate the changes of circulating monocyte subsets in AID or AID-ICH patients with pulmonary infection. The subgroups and PD-L1 expression of monocytes were measured by flow cytometry in healthy individuals (HC), new-onset AID patients (AID cohort) and AID-ICH patients with pulmonary opportunistic infection (AID-ICH cohort). Flow cytometry analysis was used to determine the distribution of monocyte subsets, including classical monocytes (CL, CD14⁺⁺CD16^-), intermediate monocytes (ITM, CD14⁺⁺CD16⁺) and non-classical monocytes (NC, CD14^+/-CD16⁺⁺), as well as the dynamic change of PD-L1 ⁺cluster among monocyte subsets. Among total monocyte, AID-ICH displayed decreased CL subset along with increased NC subset compared to HCs and AID. Regarding PD-L1 ⁺monocytes, although CL subset constituted the majority of that in HCs, AIDs and AID-ICHs, imbalance of NC/CL within PD-L1 ⁺monocytes was only noticed in AID-ICHs (<i>P</i> < 0.05). Furthermore, when AID subjects were developed into immunocompromised status (ICH), PD-L1 ⁺cluster in CL was minorly decreased (<i>P</i> > 0.05). Clinically, the lower ratio of PD-L1 ⁺cluster among CL subset (<i>P</i> < 0.05) and the less differentiated CL in PD-L1 ⁺monocytes (<i>P</i> < 0.05) was more likely to leaded to disease progression. The imbalance of circulating NC/CL subset was remarkable in immunocompromised host with pulmonary opportunistic infection, especially involvement of PD-L1⁺ cluster, which served as a potential biomarker in clinical practice.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251316152"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles of SLAMF7 in immune cells and related diseases.","authors":"Zheng Zhang, Ying Zhang, Zeyu Chen, Lin Xia","doi":"10.1177/17534259251326700","DOIUrl":"10.1177/17534259251326700","url":null,"abstract":"<p><p>Immune cells are heterogeneous and perform different functions in different microenvironment, thus playing different roles in different stages of diseases. Studies have shown that immune cells are involved in the pathogenesis of many diseases, and there is a causal association of immune cells with disease states. Signaling Lymphocyte Activation Molecule family (SLAMF) members are a newly appreciated group of specific receptors that are mainly expressed in immune cells and whose role is to regulate the function of immune cells. SLAMF7, also known as CD319, has been widely reported in multiple myeloma, and in recent years, more and more studies have shown that SLAMF7 is widely involved in the function of immune cells and the progression of breast cancer, acquired immune deficiency syndrome, systemic lupus erythematosus and other immune cells-related diseases. However, the mechanisms underlying the regulatory role of SLAMF7 on immune cells, and the impact on the progression of immune cells-related diseases remain poorly elucidated. In this review, we summarize current knowledge about the role of SLAMF7 in immune cells and related diseases such as cancer, infectious disease, autoimmune disease and atherosclerosis, and the therapeutic strategy targeting SLAMF7 is also described. By better understanding the role and regulation of SLAMF7, we hope to provide new insights and directions for improving the diagnosis and treatment of inflammation.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251326700"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of killer immunoglobulin-like receptor genotypes and haplotypes with acute lymphoblastic leukemia risk.","authors":"Jameel Al-Tamimi, Suliman Alomar, Ali Aljuaimlani, Lamjed Mansour","doi":"10.1177/17534259251314774","DOIUrl":"10.1177/17534259251314774","url":null,"abstract":"<p><strong>Background: </strong>Killer immunoglobulin-like receptors (KIRs) are key molecules used by natural killer (NK) cells to interact with target cells. These receptors exhibit extensive genotypic polymorphism which has been associated with varying outcomes in immune responses against diseases. This study aimed to investigate the relationships between <i>KIR</i> genotypes and haplotypes with acute lymphoblastic leukemia (ALL) in Saudi patients.</p><p><strong>Methods: </strong>A total of 259 Saudi subjects including 145 cases of acute lymphoblastic leukemia (ALL) and 114 healthy controls living in Riyadh were genotyped for 16 <i>KIR</i> genes and the two <i>HLA-C1</i> and <i>-C2</i> allotypes using PCR-SSP genotyping method.</p><p><strong>Results: </strong>A significant high frequency of the two inhibitory <i>KIR</i> genes; <i>2DL1</i> (OR = 2.4; <i>p</i> < 0.0001) and <i>3DL1</i>(OR = 10.87; <i>p</i> = 0.0068) in ALL compared to healthy group was observed. In contrast, the activating <i>2DS4</i> gene was significantly higher in healthy controls (OR = 0.15, <i>p</i> < 0.0001) compared to ALL patients. Haplotype analysis shows that BX haplogroup was strongly associated with the occurrence of ALL (OR = 4.39; <i>p</i> < 0.0001). Further combinatory analysis of <i>KIR</i> genes with their <i>HLA-C1</i> and <i>-C2</i> ligands demonstrated strong statistically protective effect of the <i>2DS1-C2</i> combination from ALL (OR = 0.06; <i>p</i> = 0.0003).</p><p><strong>Conclusion: </strong>This study presents strong evidence supporting the connection between certain <i>KIR</i> genotypes, haplotypes, and <i>KIR-HLA</i> combinations with acute ALL in the Saudi population. The heightened occurrence of inhibitory <i>KIR</i> genes (<i>2DL1</i> and <i>3DL1</i>) and the BX haplotype in ALL patients indicates a possible involvement of these genetic variability with the dysfunctional of NK cells in the context of ALL disease.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251314774"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of <i>Cardamine violifolia</i> on muscle protein degradation and anti-oxidative capacity in weaned piglets after Lipopolysaccharide challenge.","authors":"Nianbang Wu, Shunkang Li, Yanling Kuang, Wensheng He, Huiling Zhu, Qingyu Gao, Liping Liu, Shuiyuan Cheng, Yulan Liu, Xin Cong, Dan Wang","doi":"10.1177/17534259251322589","DOIUrl":"10.1177/17534259251322589","url":null,"abstract":"<p><p>This study aimed to investigate the impact of <i>Cardamine violifolia</i> on muscle protein degradation, the inflammatory response and antioxidant function in weaned piglets following LPS challenge. Twenty-four weaned piglets were used in a 2 × 2 factorial experiment with dietary treatment (sodium selenite or <i>Cardamine violifolia</i>) and LPS challenge. After 28 days of feeding, pigs were injected intraperitoneally with 100 μg/kg LPS or saline. Dietary supplementation with <i>Cardamine violifolia</i> mitigated the reduction in insulin and growth hormone levels induced by LPS. It also curbed the LPS-induced elevation of plasma glucagon, urea nitrogen, and creatinine concentrations. <i>Cardamine violifolia</i> reduced muscle damage caused by LPS, as evidenced by increased protein content and protein/DNA ratio and decreased TNF-α and IL-1β mRNA expression. Furthermore, <i>Cardamine violifolia</i> modulated the expression of FOXO1, FOXO4, and MuRF1 in muscle, indicative of the protective effect against muscle protein degradation. Enhanced muscle antioxidant function was observed in the form of increased T-AOC, reduced MDA concentration, and decreased mRNA expression of GPX3, DIO3, TXNRD1, SELENOS, SELENOI, SELENOO, and SEPHS2 in LPS-treated piglets. The findings suggest that <i>Cardamine violifolia</i> supplementation can effectively alleviate muscle protein degradation induced by LPS and enhance the antioxidant capacity in piglets.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251322589"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of chemical fixation with paraformaldehyde, glutardialdehyde or methanol on immunofluorescence staining of neutrophils and neutrophil extracellular traps.","authors":"Veronika Pilchová, Armina Richter, Marita Meurer, Claudia Schulz, Maren von Köckritz-Blickwede","doi":"10.1177/17534259241307563","DOIUrl":"10.1177/17534259241307563","url":null,"abstract":"<p><p>The formation of neutrophil extracellular traps (NETs) is known as an important part of the innate immune response. Still, some mechanisms regarding their formation and role during a disease are not completely understood yet. To visualize NETs by immunofluorescence microscopy, a chemical fixation is required. Therefore, this study focused on the effect of chemical fixatives on immunofluorescence staining of selected neutrophil and NET-markers, including myeloperoxidase (MPO), DNA/histone-1-complexes and citrullinated histone H3 (H3cit). Neutrophils isolated from fresh human blood were stimulated with phorbol-12-myristate 13-acetate (PMA) to induce NETs and fixed with paraformaldehyde (PFA, 4%), glutardialdehyde (GA, 5%) or methanol (MeOH, 100%) using different incubation times depending on the used fixative. We found that different fixation times with PFA had no effect on the staining intensity of MPO or DNA/histone-1-complex antibodies. For the staining of H3cit, fixation with PFA for 24 h decreased the signal intensity whereas 30 min fixation time had no effect. In contrast, glutardialdehyde induced a high amount of autofluorescence, and the fixation with 100% MeOH resulted in visible cellular damage. Therefore, we recommend 15-30 min PFA fixation for the respective stainings. Our results provide a solid basis for future experiments to study neutrophil activation and NET-formation.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259241307563"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma acute phase proteins as potential predictors of intra-amniotic inflammation and infection in preterm premature rupture of membranes.","authors":"Hee Young Cho, Kyo Hoon Park, Eunji Oh, Min Jung Lee, Bo Young Choi, Eun Mi Im","doi":"10.1177/17534259241306237","DOIUrl":"10.1177/17534259241306237","url":null,"abstract":"<p><strong>Background: </strong>We aimed to investigate the potential of altered levels of various acute phase proteins (APPs) in the plasma, either used alone or in combination with ultrasound-, clinical-, and conventional blood-based tests, for predicting the risk of intra-amniotic inflammation (IAI), microbial invasion of the amniotic cavity (MIAC), histologic chorioamnionitis (HCA), and funisitis in women with preterm premature rupture of membranes (PPROM).</p><p><strong>Methods: </strong>A total of 195 consecutive pregnancies involving singleton women with PPROM (at 23 + 0-34 + 0 weeks) who underwent amniocentesis and from whom plasma samples were obtained at amniocentesis were retrospectively included in this study. Amniotic fluid (AF) was cultured to assess the MIAC and analyzed for interleukin (IL)-6 levels to define IAI (AF IL-6 level of ≥2.6 ng/mL). The plasma concentrations of hepcidin, mannose-binding lectin (MBL), pentraxin-2, retinol-binding protein 4 (RBP4), serum amyloid A1 (SAA1), and serpin A1 were determined using ELISA. Ultrasonographic cervical length (CL), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein levels were measured. IAI/MIAC was defined as IAI, MIAC, or both.</p><p><strong>Results: </strong>Multivariate logistic regression analyses showed the following: (1) elevated plasma levels of hepcidin and SAA1 and decreased levels of RBP4 in the plasma were independently associated with IAI/MIAC and (2) decreased plasma RBP4 levels were independently associated with funisitis; however, (3) none of the plasma APPs investigated were associated with acute HCA when adjusted for baseline covariates. Using stepwise regression analysis, noninvasive prediction models comprising plasma RBP4 levels, CL, NLR, and gestational age at sampling were proposed, which provided a good prediction of IAI/MIAC and funisitis (area under the curve: 0.80 and 0.72, respectively).</p><p><strong>Conclusions: </strong>Hepcidin, RBP4, and SAA1 were identified as potential APP biomarkers in the plasma predictive of IAI/MIAC or funisitis in patients with PPROM. In particular, combination of these APP biomarkers with ultrasound-, clinical-, and conventional blood-based markers can significantly support the diagnosis of IAI/MIAC and funisitis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"17534259241306237"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}