International Journal of Immunopathology and Pharmacology最新文献

{"title":"Interleukin expression patterns and immune cell infiltration in prostate adenocarcinoma: Implications for recurrence risk.","authors":"Jialong Zhang, Cong Huang, Xu Wang, Jun He, Hongzhi Wang, Chaozhao Liang","doi":"10.1177/03946320251328476","DOIUrl":"10.1177/03946320251328476","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to comprehensively investigate the expression profiles of interleukins in prostate adenocarcinoma (PRAD) and their relationship with immune cell infiltration, tumor progression, and patient prognosis. By establishing an interleukin-related risk score, we seek to enhance the understanding of the tumor immune microenvironment and facilitate the development of tailored immunotherapeutic strategies for PRAD patients.</p><p><strong>Introduction: </strong>Interleukins can nurture a tumor promoting environment and simultaneously regulate immune cell infiltration. However, the potential roles of interleukins in the prostate adenocarcinoma immune landscape remain abstruse.</p><p><strong>Methods: </strong>We comprehensively investigated the interleukin expression patterns and tumor immune landscape of prostate adenocarcinoma patients. And explored the interleukin expression patterns with immune infiltration landscape. The interleukin score was established using LASSO cox regression analysis. Multivariate Cox regression analysis was employed to assess the prognostic value of the interleukin score.</p><p><strong>Results: </strong>We identified two distinct interleukin clusters, characterized by different immune cell infiltration, tumor promoting signaling pathways activation and prognosis. The interleukin score was established to estimate the prognosis of individual prostate adenocarcinoma (PRAD) patient. Further analysis demonstrated that the interleukin score was an independent prognostic factor of PRAD. Finally, we investigated the predictive value of interleukin score in the programmed cell death protein (PD-1) blockade therapy of patients with prostate adenocarcinoma. At the same time, the differences in related genes among different prostate cell lines were also identified.</p><p><strong>Conclusions: </strong>This study demonstrated the correlation between interleukin and tumor immune landscape in prostate adenocarcinoma. The comprehensive evaluation of interleukin expression patterns in individual prostate patients contribute to our understanding of the immune landscape and helps clinicians selecting proper immunotherapy strategies for prostate patients.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251328476"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677387","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":"Integrative analysis of crosstalk genes and diagnostic biomarkers in lupus-associated osteoporosis.","authors":"Zhihan Chen, Yunfeng Dai, Fei Gao, Jianwen Liu, Juanjuan He, Li Zhang, Yanfang Wu","doi":"10.1177/03946320251331842","DOIUrl":"https://doi.org/10.1177/03946320251331842","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) patients are at greater risk of developing osteoporosis (OP) than the general population. This study aimed to identify crosstalk genes between SLE and OP and to validate their diagnostic accuracy as biomarkers. Data analysis based on Gene Expression Omnibus (GEO) datasets was conducted. We utilized Weighted Gene Co-Expression Network Analysis (WGCNA) and differential expression analysis to identify crosstalk genes (CGs). Machine learning algorithms and consensus clustering were applied to screen shared diagnostic biomarkers and construct two predictive models featuring key genes. We also investigated potential subgroups, immune infiltration across different subtypes, and validated hub mRNAs using quantitative real-time PCR (qPCR). Molecular docking was performed to simulate the interaction of a small molecule compound with its target. We identified 19 CGs and developed two predictive models: the IL1R2-GADD45B and CHI3L1-IL1R2-SPTLC2 diagnostic score thresholds. The CHI3L1-IL1R2-SPTLC2 model showed improved predictive accuracy for lupus-associated osteoporosis. The C2 subtype was found to potentially regulate bone metabolism in SLE patients. Immune infiltration analysis indicated a strong association between CGs and multiple immunocytes, with IL1R2 being a common element in both models. Molecular docking suggests that Anakinra's therapeutic effect may involve IL1R2. Our study introduces novel diagnostic biomarkers and predictive models for lupus-associated osteoporosis, with a particular focus on IL1R2 as an innovative biomarker and therapeutic target. These are anticipated to aid early screening and risk assessment in SLE patients, pending large-scale clinical validation.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251331842"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035564","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":"Rapamycin ameliorates inflammatory pain via recovery of autophagy flux mediated by mammalian target of rapamycin (mTOR) signaling pathway in the rat spinal cord.","authors":"Jiawei Zhang, Shi Chen, Rongyi Zhang, Xiaoting Zheng, Chang Liu, Jiqian Zhang, Lei Zhang, Zhilai Yang, Likui Wang","doi":"10.1177/03946320251317284","DOIUrl":"10.1177/03946320251317284","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the effect of rapamycin on inflammatory pain in rats.</p><p><strong>Introduction: </strong>Inflammatory pain is a kind of pathological pain caused by inflammatory mediators or factors such as TNF-α (Tumor Necrosis Factor-α), IL-1β (Interleukin-1β), and IL-6 (Interleukin-6). NSAIDs and opioid analgesics are commonly used for relieving inflammatory pain, but the side effects limit their clinical application. New drugs based on new mechanisms for inflammatory pain are urgently needed. Autophagy is an evolutionarily conserved homeostatic process for lysosomal degradation of intracellular components. Recent reports indicate the involvement of autophagy in the development and maintenance of neuropathic pain, but the role of autophagy in inflammatory pain still needs to be explored.</p><p><strong>Methods: </strong>The pain-related behaviors of rats were studied by paw withdrawal threshold and paw withdrawal latency. The autophagy level of the rat spinal cord was detected by western blots. The concentrations of TNF-α, IL-1β, and IL-6 were detected by ELISA.</p><p><strong>Results: </strong>We found that the paw withdrawal threshold and paw withdrawal latency were both significantly decreased after CFA (Complete Freund's Adjuvant) injection, accompanied by the activation of mTOR signaling pathway and the inhibited autophagy flux in the spinal cord. And inflammatory cytokines were increased in the spinal cord after CFA injection. Then, we studied the effect of rapamycin on CFA-induced inflammatory pain in rats, and found that rapamycin restored the autophagy flux and significantly reduced mechanical allodynia and thermal hyperalgesia. In addition, rapamycin significantly decreased the levels of TNF-α, IL-1β, and IL-6 after CFA injection in the spinal cord.</p><p><strong>Conclusion: </strong>Our results suggested that rapamycin might be a promising candidate for the treatment of inflammatory pain by restoring the autophagy flux in the spinal cord.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251317284"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081697","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":"Dissociation between the expression of cGAS/STING and a senescence-associated signature in colon cancer.","authors":"Sofian Al Shboul, Ola Abu Al Karsaneh, Moath Alrjoub, Mohammad Al-Qudah, Mohammed El-Sadoni, Ahmad Alhesa, Mohannad Ramadan, Marwa Barukba, Esraa Fares Al-Quran, Amr Masaadeh, Farah N Almasri, Uruk Shahin, Moureq R Alotaibi, Mohammad Al-Azab, Ashraf I Khasawneh, Tareq Saleh","doi":"10.1177/03946320251324821","DOIUrl":"10.1177/03946320251324821","url":null,"abstract":"<p><strong>Objective: </strong>The effect of the cGAS/STING pathway on antitumor immunity and its connection to senescence in vivo necessitates further investigation.</p><p><strong>Introduction: </strong>Cellular senescence and its secretory phenotype (the SASP) are implicated in modulating the immune microenvironment of cancer possibly through the cGAS/STING pathway.</p><p><strong>Methods: </strong>Gene expression data from paired colon cancer and adjacent non-malignant mucosa (98 patients, <i>n</i> = 196 samples; 65 patients, <i>n</i> = 130 samples) were analyzed for cGAS/STING and a senescence signature. Immunohistochemistry assessed cGAS/STING protein expression in 124 colorectal samples.</p><p><strong>Results: </strong>Approximately one-quarter of patients displayed senescence profiles in both gene sets, yet without significantly correlating with cGAS/STING expression. Notably, cGAS expression was higher than STING in tumor tissue compared to non-malignant colonic mucosa. Protein analysis showed 83% positive cGAS expression and 39% positive STING expression, with discrepancies in expression patterns. Additionally, 15% of samples lacked both markers, while 35% exhibited positive staining for both. No significant correlations were found between cGAS/STING status and tumor stage, patient age, lymphovascular invasion, or lymph node involvement.</p><p><strong>Conclusions: </strong>Our findings demonstrate significant senescence marker expression in colorectal cancer samples but with no correlation with cGAS/STING.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251324821"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606156","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":"Chemotherapy elevates cell surface PD-L1 and MHC-I expression in apoptotic gastric cancer cells.","authors":"You-Syuan Lou, Xu-Chen Liu, Chih-Cheng Cheng, Yi-Hsuan Yin, Tzu-Cheng Chien, Pei-Ling Hsu, Chu-Wan Lee, Hsin-Hsien Yu, Bor-Chyuan Su","doi":"10.1177/03946320251338662","DOIUrl":"10.1177/03946320251338662","url":null,"abstract":"<p><strong>Background: </strong>The programmed cell death-ligand 1 (PD-L1) combined positive score is used as a patient selection tool and predictive factor for anti-programmed cell death-1 (PD-1)/PD-L1 therapy in gastric cancer. However, the expression of PD-L1 and major histocompatibility complex class I (MHC-I) can be affected by conventional treatment approaches.</p><p><strong>Objective: </strong>In this study, we examined the effects of chemotherapy on surface PD-L1 and surface MHC-I expression in living and apoptotic gastric cancer cells. AGS (moderately differentiated) and SNU-1 (poorly differentiated) cells were treated 5-Fluorouracil (5-Fu), cisplatin, mitomycin c (MMC), and FOLFOX (5-Fu, leucovorin, and oxaliplatin).</p><p><strong>Methods: </strong>To quantify the expression levels of surface PD-L1 or surface MHC-I on living and apoptotic cells, the cells were co-stained with annexin V and PD-L1 or MHC-I antibodies. The percentages of single positive (annexin V-negative, PD-L1-positive; annexin V-negative, MHC-I-positive) and double positive (annexin V-positive, PD-L1-positive; annexin V-positive, MHC-I-positive) cells were analyzed by flow cytometry.</p><p><strong>Results: </strong>Every tested chemotherapeutic agent increased the levels of surface PD-L1 and surface MHC-I, although the extents of increase differed in AGS and SNU-1 cells. In AGS cells, 5-Fu caused the largest increases in surface PD-L1 and surface MHC-I. However, 5-Fu caused the weakest increases in surface PD-L1 and surface MHC-I in SNU-1 cells. Notably, chemotherapy-mediated increases in surface PD-L1 and surface MHC-I mostly occurred on apoptotic cells.</p><p><strong>Conclusion: </strong>Our findings reveal that chemotherapy mainly increases surface PD-L1 and surface MHC-I on apoptotic gastric cancer cells.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251338662"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086609","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":"Molecular characterization and antibiotic susceptibility of methicillin-resistant <i>Staphylococcus aureus</i> in immunocompromised cancer patients.","authors":"Samah Radwan, Dalia Y Kadry, Rana Hamdy, Mahmoud M Kamel, Abrar S Alsulami, Ahmed S Abdel-Moneim, Dina M Elkhashab","doi":"10.1177/03946320251352258","DOIUrl":"https://doi.org/10.1177/03946320251352258","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to analyze <i>MRSA</i> isolates from pediatric cancer patients, determine the prevalence of PVL genes and assess their clinical implications.</p><p><strong>Introduction: </strong>Methicillin-resistant <i>Staphylococcus aureus (MRSA)</i> infections pose significant challenges in pediatric oncology settings. Understanding the prevalence, genotypic characteristics, and antibiotic resistance patterns of <i>MRSA</i> aids in improving patients' outcomes.</p><p><strong>Methods: </strong>A total of 120 <i>S. aureus</i> isolates from patients receiving chemotherapy for treatment of malignant diseases and developing BSIs during febrile episodes were examined. Isolates were identified using Gram staining, biochemical tests, and VITEK 2-Compact 15. Antimicrobial susceptibility was tested using the Kirby-Bauer disk diffusion method. Molecular characterization included PCR assays for <i>16S rDNA</i>, multiplex PCR for <i>femA, mecA</i>, and <i>PVL</i> genes, and <i>SCC_mec</i> type.</p><p><strong>Results: </strong>Out of 120 isolates of <i>Staphylococcus aureus, 97</i> (80%) isolate possessed mecA gene and were identified as <i>MRSA, MRSA</i> bacteremia harboring <i>PVL</i> gene was detected in cancer patients in Egypt at 26.8% of <i>MRSA</i> isolates. The study identified a higher fatality rate in patients aged 6-10 years (26.7%) compared to other age groups (<i>p</i> < 0.044). Deceased patients exhibited higher leukocyte counts and lower platelet counts. Solid tumor patients had significantly higher neutrophil and monocyte counts. <i>Type II</i> of <i>SCC_mec</i> correlated with survival and mortality, with the <i>PVL</i> gene being a significant factor. <i>Type III</i> showed a higher prevalence of <i>femA and mecA</i> among survivors, while <i>Type IVb</i> was associated with better outcomes. Antibiotic susceptibility revealed high resistance to cefoxitin, cefepime, and Tazocin, but better sensitivity to ciprofloxacin and gentamicin, particularly in <i>Types IV</i> and <i>V</i>.</p><p><strong>Conclusion: </strong>The study highlights the age-related fatality differences and the impact of HCV infection on survival rates. Hematologic parameters and <i>SCC_mec types</i> play a crucial role in patient outcomes. The observed antibiotic resistance patterns necessitate the need for targeted therapies based on <i>MRSA SCC_mec types</i>.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251352258"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975178","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":"Role of β and α1-adrenoceptors in pancreatic regulation of glucose homeostasis, apoptosis, and fibrosis in dexamethasone-treated rats: A new insight into β-arrestin2 crosstalk with cAMP, PKA-ERK1/2-CREB, and PKB-FOXO1 signaling pathways.","authors":"Nehal S Wahba, Ahmed Abdelfattah-Hassan, Dalia A Hemead, Alaa S Wahba, Islam A A E-H Ibrahim, Mona F Mahmoud, Maryam A Al-Ghamdi, Etimad Huwait, Mostafa E El-Naggar","doi":"10.1177/03946320251365089","DOIUrl":"10.1177/03946320251365089","url":null,"abstract":"<p><strong>Objective: </strong>The current study aimed to investigate the role of β and α1-adrenoceptors in pancreatic regulation of glucose homeostasis, apoptosis, and fibrosis in a rat model of dexamethasone-induced insulin resistance.</p><p><strong>Introduction: </strong>Insulin resistance is a hallmark of metabolic syndrome and is often linked to glucocorticoid excess. β- and α1-adrenoceptors are key modulators of glucose metabolism and tissue remodeling, yet their roles in pancreatic dysfunction under metabolic stress remain incompletely understood. Emerging evidence highlights β-arrestin2 as a key mediator of apoptosis and fibrosis beyond classical G protein signaling.</p><p><strong>Methods: </strong>Insulin resistance was induced in rats by subcutaneous dexamethasone (10 mg/kg/day) for 7 days. The therapeutic effects of carvedilol, phenylephrine, phenylephrine + carvedilol, propranolol, doxazosin, and doxazosin + propranolol were evaluated in relation to glucose homeostasis and pancreatic apoptotic/fibrotic signaling.</p><p><strong>Results and conclusion: </strong>Dexamethasone impaired glucose homeostasis, expanded islet mass, and triggered pancreatic cell apoptosis and fibrosis via upregulated BAX/Bcl-2 expression ratio, downregulated cAMP, upregulated PKA, ERK1/2, and CREB expression with elevated PKB activity and reduced FOXO1 expression. % Level of β-arrestin2 was reduced in pancreatic islets and elevated in exocrine pancreas in relation to the aforementioned modulations. Blockade of β- or α1-adrenoceptors significantly ameliorated these effects, with combined blockade yielding superior benefits. Carvedilol's effects were largely β-mediated, with minor α1 involvement. Low-dose phenylephrine yielded modest improvement, supporting a context-dependent, protective role of α1-adrenoceptor activation during metabolic stress. The dependence of drugs' effects on β-arrestin2 highlights its potential as a central regulator of pancreatic remodeling and a promising target in IR-linked pathologies.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251365089"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201959","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":"Unveiling lymphocyte dynamics: Navigating postoperative immune landscapes in gastric cancer patients undergoing laparoscopic D2 gastrectomy.","authors":"Chun Gao, Li Zhu, Yi Xin Tong, Sheng Zhang","doi":"10.1177/03946320251352344","DOIUrl":"10.1177/03946320251352344","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with locally advanced gastric cancer often face postoperative complications and insufficient short-term outcomes. Understanding the changes in peripheral lymphocyte subsets following laparoscopic D2 gastrectomy is critical to addressing these challenges and enhancing postoperative recovery.</p><p><strong>Objective: </strong>This study investigates the dynamics of peripheral lymphocyte subsets in gastric cancer patients post-laparoscopic D2 gastrectomy. Our goal is to identify factors contributing to postoperative reductions in these immune cells, thereby improving management strategies.</p><p><strong>Methods: </strong>We retrospectively analyzed clinicopathological data from 169 gastric cancer patients, focusing on perioperative lymphocyte subset variations. Utilizing univariate and multivariate analyses, we identified factors significantly influencing lymphocyte reductions after surgery.</p><p><strong>Results and conclusion: </strong>By postoperative day 7, we observed median decreases in T cells, B cells, NK cells, and memory T cells of -26.1%, -30.8%, -44.8%, and -2.3%, respectively. In contrast, naive T cells and regulatory T cells increased by 6.0% and 15.0%. Thymosin alpha 1 (Tα1) treatment proved to be a protective factor, significantly reducing the decline in T and B cell counts (<i>p</i> = 0.05). Multivariate analysis identified higher Interleukin-1β levels (HR = 3.66, <i>p</i> = 0.01), longer operation times (HR = 2.98, <i>p</i> = 0.02), and Tα1 therapy (HR = 0.15, <i>p</i> = 0.01) as independent predictors of T cell reduction. These findings highlight Tα1's potential as a therapeutic intervention to mitigate lymphocyte depletion, suggesting its incorporation into postoperative care could enhance immune recovery and patient outcomes. This study illuminates key immunological changes following gastric cancer surgery, offering pathways to improve postoperative management and patient health.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251352344"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620942","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":"A new heterozygous TYK2 gene mutation: Case report and review of the literature.","authors":"Lei Xie, Xinyue Hu, Hejing Wang, Juntao Feng, Ruoxi He","doi":"10.1177/03946320251351138","DOIUrl":"10.1177/03946320251351138","url":null,"abstract":"<p><p>Tyrosine kinase 2 (TYK2) deficiency is a rare primary immunodeficiency disease (PID). Patients carry TYK2 gene mutations and suffer from recurrent infections by intracellular pathogens, including mycobacteria. Delayed diagnosis often hinders timely and effective treatment, resulting in poor prognosis. In this study, we report a newly discovered TYK2 deficiency patient with recurrent pulmonary infections. The patient, a 27-year-old Chinese man with a history of tuberculosis, presented with recurrent cough, phlegm, and purulent sputum. Lung CT scan showed bronchiectasis with concomitant infection. Next-generation sequencing (NGS) identified Mycobacterium gordonae and Mycobacterium chelonae in lung, along with heterozygous c.997G>A&c.10C>T (p.V333M&p.R4C) mutation in TYK2. Further pathogenicity prediction analysis via dbNSFP (v5.1a) suggested the potential pathogenicity of this genetic variant. Additionally, TYK2 mRNA expression in peripheral blood mononuclear cells (PBMCs) also decreased significantly. Following anti-infective treatment, the patient improved and was discharged with regular human immunoglobulin infusion. However, the patient unfortunately succumbed to disease exacerbation in October 2021, 15 months after diagnosis. Furthermore, a literature review was conducted on cases of TYK2 deficiency. Previous studies have identified 24 mutation sites within TYK2 gene, which impair immune function and lead to early-onset recurrent infections. These mutations contribute to clinical heterogeneity, with the most common manifestation being recurrent infections by opportunistic pathogens, particularly mycobacteria. Our discovery of a novel TYK2 mutation expands the gene's mutation spectrum. Analyzing the characteristics of reported cases enhances understanding of TYK2 deficiency's clinical manifestations and facilitates early diagnosis of this rare condition.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251351138"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530456","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":"Protein-losing enteropathy as initial presentation of pediatric systemic lupus erythematosus: A rare case report from Vietnam and literature review.","authors":"Cong Mai Thanh, Phuoc Nguyen Trong, Nam Nguyen Thanh","doi":"10.1177/03946320251358304","DOIUrl":"10.1177/03946320251358304","url":null,"abstract":"<p><p>Protein-losing enteropathy (PLE) is a rare but recognized manifestation of systemic lupus erythematosus (SLE). As an initial presentation of SLE, PLE is exceptionally uncommon, particularly in pediatric patients. We report the case of a 15-year-old Vietnamese girl with no significant past medical or family history, who presented with PLE as the initial manifestation of SLE. Clinical features included bilateral eyelid and lower extremity edema, ascites, and hypoalbuminemia, in the absence of nephrotic-range proteinuria, hepatic dysfunction, or malnutrition. Stool α1-antitrypsin concentration was markedly elevated at >231 mg/dL (normal <26.8 mg/dL), supporting the diagnosis of PLE in conjunction with clinical features and therapeutic response. Immunological evaluation revealed positive antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, and lupus anticoagulant, hypocomplementemia, along with proteinuria equivalent to >0.5 g/24 h, fulfilling the 2019 EULAR/ACR classification criteria for SLE. The patient also developed cerebral venous sinus thrombosis. Treatment with corticosteroids, hydroxychloroquine, and warfarin resulted in significant clinical improvement. At 7 months of follow-up, she remained clinically stable, with normalized serum albumin levels and resolution of thrombosis. This case highlights the challenges of diagnosing PLE as an initial symptom of SLE in resource-limited settings. Heightened awareness of this rare presentation can facilitate early diagnosis and optimal management, improving patient outcomes.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"39 ","pages":"3946320251358304"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668728","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}