Hasil untuk "Immunologic diseases. Allergy"

P. Gell, R. Coombs

Yang X, Huang S, Wang Y et al.

Xinyu Yang,1– 3,* Sen Huang,1– 3,* Yuxin Wang,1– 3 Jing Yuan,1– 3 Xiaoli Yao1– 3 1Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoli Yao, Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China, Email yaoxiaol@mail.sysu.edu.cnPurpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Progressive loss of motor neuron function and disruption of the blood-brain barrier are key features of ALS. Under the influence of chemokines, peripheral immune cells migrate into the central nervous system, thereby affecting the neuronal microenvironment. The aim of this study is to classify ALS based on the immune characteristics of peripheral blood in patients with the disease, and to construct prognostic models.Patients and Methods: A total of 397 ALS patients and 645 healthy controls (GSE112676 and GSE112680) were included. ALS chemotactic subtypes were constructed based on differentially expressed genes of chemokine and chemokine receptors (CCRs). The Cibersort algorithm was used to investigate the abundance of immune cells in peripheral blood. Univariate Cox regression analysis was performed to screen for CCRs genes, clinical characteristics, and immune cells associated with prognosis. Prognostic models were constructed based on these variables. Finally, external validation was conducted using samples from ALS patients diagnosed at the First Affiliated Hospital of Sun Yat-sen University.Results: There were significant differences in the abundance of peripheral immune cells between ALS patients and healthy controls. 17 CCRs genes were identified as differentially expressed. CCL23, CCR8, CXCR4, site of onset, age of onset, and “CD4 naive T cells” were demonstrated to be significantly correlated with survival time. Two chemotactic subtypes were established. Eight prognostic models could distinguish between high-risk and low-risk ALS patients. At year five, the areas under the receiver operating characteristic curves for the PlsRcox, Coxboost, and Xgboost algorithms were 0.747, 0.733, and 0.728, respectively. External test sets successfully validated these results.Conclusion: ALS patients exhibit peripheral immune abnormalities. Peripheral immune status could be used to distinguish ALS subtypes and construct prognostic models. Understanding peripheral immune changes in ALS patients may inform potential immunotherapies.Keywords: amyotrophic lateral sclerosis, peripheral immunity, chemokine, chemokine receptor

Zimeng Cai, Mina Kozai, Hironobu Mita et al.

BackgroundMemory CD8+ T cells sense inflammation and rapidly produce interferon-γ (IFN-γ) independent of cognate antigens. This innate-like property, called bystander activation, is involved in early host defense before the antigen-specific memory response. However, the molecular mechanisms underlying this activation remain unknown. Retinoic acid receptor-related orphan receptor α (RORα) belongs to the nuclear receptor family and regulates gene transcription in ligand-dependent manner. Although RORα is highly expressed in memory CD8+ T cells, its functional relevance has not been investigated.MethodsPrimary and secondary memory T cells that are sufficient or deficient of RORα were induced by adoptive transfer of naïve OT-I T cells to recipient mice and subsequent infection with Listeria monocytogenes expressing ovalbumin (LM-OVA). RORα expression in memory T cells was examined by quantitative PCR. The target genes of RORα in memory T cells were explored by RNA-sequencing and verified by RORα overexpression in postactivated T cells. The impact of RORα-deficiency on bystander activation was assessed by stimulating memory T cells with inflammatory cytokines in vitro or injecting lipopolysaccharide (LPS) into mice bearing memory T cells.ResultsRORα expression was remarkably elevated in secondary memory CD8+ T cells along with the enrichment of effector-like memory T cells. RORα primarily acted as a transcription factor in regulating the gene expression of the TL1A receptor. RORα deficiency abrogated the IFN-γ production by memory CD8+ T cells in response to IL-12 + TL1A in vitro and diminished the bystander response to LPS-induced inflammation in vivo.ConclusionThis study revealed a regulatory mechanism of bystander activation. The findings also improve our understanding of how memory T cells increase their immediate protective capacity through repeated infections and vaccinations.

Yumeng Li, Zhiheng Lin, Guangyao Lin et al.

BackgroundCervical cancer’s tumor microenvironment (TME) was composed of a diverse array of immune cells that significantly influence tumor progression and response to treatment. Recent advancements in multi-omics and single-cell sequencing had provided valuable insights into the cellular heterogeneity and immune landscape of the TME, revealing critical interactions that shape tumor behavior and therapy outcomes.MethodThis study used multi-omics and single-cell sequencing to explore the immune landscape, cellular heterogeneity, and drug sensitivity in cervical cancer, focused on tumor subtypes and their interactions with immune cells, and aimed to understand therapy responses.ResultsThe research presented a thorough single-cell analysis of cervical cancer, identified distinct tumor epithelial cell (EPC) subtypes, and explored their roles in tumor progression, immune evasion, and therapeutic response. It underscored the potential of tumor EPCs as valuable biomarkers for prognosis and as targets for personalized treatment approaches.ConclusionThe immune landscape of cervical cancer and its interaction with tumor endothelial progenitor cells played crucial roles in determining the tumor’s progression and response to therapy. The classification of tumor subtypes based on immune characteristics and drug sensitivity was critical for personalized treatment. The identification of TSPAN1 as key biomarkers provided insight into tumor biology and potential therapeutic targets. Our findings emphasized the need for combining immune checkpoint modulation with precise drug sensitivity analysis to optimize treatment strategies, particularly in advanced cervical cancer.

Xu Tong, Tao Zhan, Xiaoqin Dong et al.

Since the approval for the treatment of melanoma in 2014, immune checkpoint inhibitors (ICIs) have revolutionized the therapy pattern across various malignancies. Coinciding with their frequent usage, their adverse effects, including fever, cannot be neglected. In the context of cancer diseases and cancer treatments, fever of unknown origin (FUO), which has long posed a challenge for clinicians in terms of diagnosis and management, brings forth new connotation and significance. In this paper review, we present the concept of ICIs-associated FUO, consider activated immune system and elevated cytokines as common mechanisms by which ICIs induce fever and various immune-related adverse events (irAEs), summarize and compare the primary etiologies of ICI-associated FUO, and compare it with conventional types of FUO.

Chun Zhang, Sun Chen, Yan Bian et al.

Abstract Objectives For children with Kawasaki disease (KD) at high risk of developing coronary artery lesions and requiring retreatment with intravenous immunoglobulin (IVIG), the availability of accurate prediction models remains limited because of inconsistent variables and unsatisfactory prediction results. We aimed to construct models to predict patient's probability of IVIG retreatment combining children's individual inflammatory characteristics. Methods Clinical manifestations and laboratory examinations of 266 children with KD were retrospectively analysed to build a development cohort data set (DC) and a validation cohort data set (VC). In the DC, binary logistic regression analyses were performed using R language. Nomograms and receiver operating curves were plotted. The concordance index (C index), net reclassification index, integrated discrimination improvement index and confusion matrix were applied to evaluate and validate the models. Results Models_5V and _9V were established. Both contained variables including the percentages of CD8+ T cells, CD4+ T cells, CD3+ T cells, levels of interleukin (IL)‐2R and CRP. Model_9V additionally included variables for IL‐6, TNF‐α, NT‐proBNP and sex, with a C index of 0.86 (95% CI 0.79–0.92). When model_9V was compared with model_5V, the NRI and IDI were 0.15 (95% CI 0.01–0.30, P < 0.01) and 0.07 (95% CI 0.02–0.12, P < 0.01). In the VC, the sensitivity, specificity and precision of model_9V were 1, 0.875 and 0.667, while those of model_5V were 0.833, 0.875 and 0.625. Conclusion Model_9V combined cytokine profiles and lymphocyte subsets with clinical characteristics and was superior to model_5V achieving satisfactory predictive power and providing a novel strategy early to identify patients who needed IVIG retreatment.

Aldo Torre, Froylan David Martínez‐Sánchez, Sofía Mercedes Narvaez‐Chávez et al.

Abstract Background Pirfenidone has demonstrated significant anti‐inflammatory and antifibrotic effects in both animal models and some clinical trials. Its potential for antifibrotic activity positions it as a promising candidate for the treatment of various fibrotic diseases. Pirfenidone exerts several pleiotropic and anti‐inflammatory effects through different molecular pathways, attenuating multiple inflammatory processes, including the secretion of pro‐inflammatory cytokines, apoptosis, and fibroblast activation. Objective To present the current evidence of pirfenidone's effects on several fibrotic diseases, with a focus on its potential as a therapeutic option for managing chronic fibrotic conditions. Findings Pirfenidone has been extensively studied for idiopathic pulmonary fibrosis, showing a favorable impact and forming part of the current treatment regimen for this disease. Additionally, pirfenidone appears to have beneficial effects on similar fibrotic diseases such as interstitial lung disease, myocardial fibrosis, glomerulopathies, aberrant skin scarring, chronic liver disease, and other fibrotic disorders. Conclusion Given the increasing incidence of chronic fibrotic conditions, pirfenidone emerges as a potential therapeutic option for these patients. However, further clinical trials are necessary to confirm its therapeutic efficacy in various fibrotic diseases. This review aims to highlight the current evidence of pirfenidone's effects in multiple fibrotic conditions.

Roberto Fuentes, Leire Aguinagalde, Carlo Pifferi et al.

Vaccine adjuvants are key for optimal vaccine efficacy, increasing the immunogenicity of the antigen and potentiating the immune response. Saponin adjuvants such as the carbohydrate-based QS-21 natural product are among the most promising candidates in vaccine formulations, but suffer from inherent drawbacks that have hampered their use and approval as stand-alone adjuvants. Despite the recent development of synthetic derivatives with improved properties, their full potential has not yet been reached, allowing the prospect of discovering further optimized saponin variants with higher potency. Herein, we have designed, chemically synthesized, and immunologically evaluated novel oxime-derivatized saponin adjuvants with targeted structural modifications at key triterpene functionalities. The resulting analogues have revealed important findings into saponin structure-activity relationships, including adjuvant mechanistic insights, and have shown superior adjuvant activity in terms of significantly increased antibody response augmentation compared to our previous saponin leads. These newly identified saponin oximes emerge as highly promising synthetic adjuvants for further preclinical development towards potential next generation immunotherapeutics for future vaccine applications.

Hamid Khakshoor, Hamid Gharaei, Malihe Nikandish

Two cases are presented with corneal ectasia after photorefractive keratectomy (PRK). Case 1 is a 24-year-old man with manifest refractions of -6.0 DS, -3.0 DC, axis 180° in the right eye and -4.50 DS, -4.0 DC, axis 160° in the left eye respectively with a symmetric bow-tie pattern bilaterally, without any evidence of keratoconus on corneal topography preoperatively. Ectasia occurred 10 months after surgery in the right eye.Case 2 is a 20-year-old man with an attempted correction of −6.25 DS, -2.25 DC, axis 30° in the right eye, and −6.25 DS, −2.25 DC, axis 150° in the left eye. Thinnest central corneal thickness was 498µm and 499µm in the right and left eyes, respectively. Total ablation depth was 137 µm in the right eye and 136 µm in the left eye. 38 months after surgery ectasia developed in the left eye. Two patients had no family history suspicious for keratoconus.Copyright: 2021 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Elene A. Clemens, Beth C. Holbrook, Brendan McNeilly et al.

Abstract The newborn immune system is characterized by diminished immune responses that leave infants vulnerable to virus-mediated disease and make vaccination more challenging. Optimal vaccination strategies for influenza A virus (IAV) in newborns should result in robust levels of protective antibodies, including those with broad reactivity to combat the variability in IAV strains across seasons. The stem region of the hemagglutinin (HA) molecule is a target of such antibodies. Using a nonhuman primate model, we investigate the capacity of newborns to generate and maintain antibodies to the conserved stem region following vaccination. We find adjuvanting an inactivated vaccine with the TLR7/8 agonist R848 is effective in promoting sustained HA stem-specific IgG. Unexpectedly, HA stem-specific antibodies were generated with a distinct kinetic pattern compared to the overall response. Administration of R848 was associated with increased influenza-specific T follicular helper cells as well as Tregs with a less suppressive phenotype, suggesting adjuvant impacts multiple cell types that have the potential to contribute to the HA-stem response.

Davari DR, Nieman EL, McShane DB et al.

Danielle R Davari, Elizabeth L Nieman, Diana B McShane, Dean S Morrell Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill, NC, USACorrespondence: Dean S MorrellDepartment of Dermatology, University of North Carolina School of Medicine, 410 Market Street Suite 400, Chapel Hill, NC 27516, USATel +1 984 974 3900Fax +1 984 974 3692Email morrell@med.unc.eduAbstract: Atopic dermatitis (AD) is a common disease of childhood, and infantile AD may manifest from birth to 2 years. Guidelines for the management of infantile AD are lacking, and our aim is to provide a comprehensive review of best practices and possible interventions. We will focus on topical therapy, since the use of systemic immunomodulating agents in infantile AD is rarely advised. Topical agents include emollients, topical corticosteroids (TCS), topical calcineurin inhibitors (TCIs), and phosphodiesterase 4 (PDE-4) inhibitors. We will also provide a brief overview of promising emerging therapies currently under investigation in the pediatric population.Keywords: eczema, pediatric, infants, treatment

Guang-Ang Tian, Chun-Jie Xu, Kai-Xia Zhou et al.

Accumulating evidence has pointed out that metastasis is the leading cause of death in several malignant tumor, including CRC. During CRC, metastatic capacity is closely correlated with reprogrammed energy metabolism. Mitochondrial Pyruvate Carrier 1 (MPC1), as the carrier of transporting pyruvate into mitochondria, linked the glycolysis and TCA cycle, which would affect the energy production. However, the specific role of MPC1 on tumor metastasis in CRC remains unexplored. Here, by data mining of genes involved in pyruvate metabolism using the TCGA dataset, we found that MPC1 was significantly downregulated in CRC compared to nontumor tissues. Similar MPC1 expression pattern was also found in multiple GEO datasets. IHC staining in both human sample and AOM/DSS induced mouse CRC model revealed significant downregulation of MPC1. What is more, we found that MPC1 expression was gradually decreased in normal tissue, primary CRC, and metastasis CRC. Additionally, poor prognosis emerged in the MPC1 low expression patients, especially in patients with metastasis. Following, functional tests showed that MPC1 overexpression inhibited the motility of CRC cells in vitro and MPC1 silencing enhanced liver metastases in vivo. Furthermore, we uncovered that decreased MPC1 activated the Wnt/β-catenin pathway by promoting nuclear translocation of β-catenin to mediate the expression of MMP7, E-cadherin, Snail1, and myc. Collectively, our data suggest that MPC1 has the potential to be served as a promising biomarker for diagnosis and a therapeutic target in CRC.

T. Holzhauser

In food allergy, a common immunological disease with a potentially severe outcome, a causative cure is not available. Correct ingredient labeling and risk assessment of unlabeled allergen cross-contact is a prerequisite for effective allergen avoidance. Specific and sensitive analytical methods, which allow for unequivocal identification and accurate quantification of allergenic components, are important tools in allergen risk management. Both protein- and DNA-based methods are in place and reveal pros and cons depending upon the application and individual analytical question. This perspective highlights relevant molecular aspects and discusses, especially, opportunities for the application of DNA-based methods for the detection of allergenic foods.

Yuka Nadai, Yuka Nadai, Kathrin Held et al.

Background: A better understanding of the parameters influencing vaccine-induced IgG recognition of individual antigenic regions and their variants within the HIV Envelope protein (Env) can help to improve design of preventive HIV vaccines.Methods: Env-specific IgG responses were mapped in samples of the UKHVC003 Standard Group (UK003SG, n = 11 from UK) and TaMoVac01 (TMV01, n = 17 from Tanzania) HIV vaccine trials. Both trials consisted of three immunizations with DNA, followed by two boosts with recombinant Modified Vaccinia Virus Ankara (MVA), either mediating secretion of gp120 (UK003SG) or the presentation of cell membrane bound gp150 envelopes (TMV01) from infected cells, and an additional two boosts with 5 μg of CN54gp140 protein adjuvanted with glucopyranosyl lipid adjuvant (GLA). Env immunogen sequences in UK003SG were solely based on the clade C isolate CN54, whereas in TMV01 these were based on clades A, C, B, and CRF01AE. The peptide microarray included 8 globally representative Env sequences, CN54gp140 and the MVA-encoded Env immunogens from both trials, as well as additional peptide variants for hot spots of immune recognition.Results: After the second MVA boost, UK003SG vaccinees almost exclusively targeted linear, non-glycosylated antigenic regions located in the inter-gp120 interface. In contrast, TMV01 recipients most strongly targeted the V2 region and an immunodominant region in gp41. The V3 region was frequently targeted in both trials, with a higher recognition magnitude for diverse antigenic variants observed in the UK003SG (p &lt; 0.0001). After boosting with CN54gp140/GLA, the overall response magnitude increased with a more comparable recognition pattern of antigenic regions and variants between the two trials. Recognition of most immunodominant regions within gp120 remained significantly stronger in UK003SG, whereas V2-region recognition was not boosted in either group.Conclusions: IgG recognition of linear antigenic Env regions differed between the two trials particularly after the second MVA boost. Structural features of the MVA-encoded immunogens, such as secreted, monomeric gp120 vs. membrane-anchored, functional gp150, and differences in prime-boost immunogen sequence variability most probably contributed to these differences. Prime-boosting with multivalent Env immunogens during TMV01 did not improve variant cross-recognition of immunodominant peptide variants in the V3 region.

Mitra Shourian, Mitra Shourian, Ben Ralph et al.

Interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) are pro-inflammatory cytokines that are induced after Cryptococcus neoformans infection and activate the interleukin-1 receptor type I (IL-1RI). To establish the role of IL-1RI signaling in protection against cryptococcal infection, we analyzed wild-type (WT) and IL-1RI-deficient (IL-1RI−/−) mice on the BALB/c background. IL-1RI−/− mice had significantly reduced survival compared to WT mice after intratracheal challenge with C. neoformans 52D. Microbiological analysis showed a significant increase in the lung and brain fungal burden of IL-1RI−/− compared to WT mice beginning at weeks 1 and 4 postinfection, respectively. Histopathology showed that IL-1RI−/− mice exhibit greater airway epithelial mucus secretion and prominent eosinophilic crystals that were absent in WT mice. Susceptibility of IL-1RI−/− mice was associated with significant induction of a Th2-biased immune response characterized by pulmonary eosinophilia, M2 macrophage polarization, and recruitment of CD4+ IL-13+ T cells. Expression of pro-inflammatory [IL-1α, IL-1β, TNFα, and monocyte chemoattractant protein 1 (MCP-1)], Th1-associated (IFNγ), and Th17-associated (IL-17A) cytokines was significantly reduced in IL-1RI−/− lungs compared to WT. WT mice also had higher expression of KC/CXCL1 and sustained neutrophil recruitment to the lung; however, antibody-mediated depletion of these cells showed that they were dispensable for lung fungal clearance. In conclusion, our data indicate that IL-1RI signaling is required to activate a complex series of innate and adaptive immune responses that collectively enhance host defense and survival after C. neoformans 52D infection in BALB/c mice.

Alberto Vieira-Hernández, Arnaldo Capriles-Hulett, Mario Sánchez-Borges et al.

Background: High-dose aqueous subcutaneous immunotherapy is a validated and effective administration route for house dust mite and pollen allergens. Objective: A proof-of-concept study using intradermal immunotherapy (IDIT) with low-dose house dust mite allergens (Dermatophagoides pteronyssinnus/Dermatophagoides farinae [Dp/Df] and Blomia tropicalis [Bt]) was carried out in children with allergic rhinitis symptomatic upon exposure to house dust. Methods: Eight immunotherapy-naïve patients with positive prick skin tests and specific serum IgE to a Dp/Df mixture and to Bt were weekly administered 0.05 mL of an IDIT consisting of a phenolyzed albumin-saline preparation containing low-dose dust mites (8.3 AU [5 ng] of Dp/Df and 2.5 DBU of Bt), for 3 months. Nasal (Total Nasal Symptom Score) and facial symptoms (Visual Analog Scale) were recorded 2 weeks prior to treatment and once weekly during its course. Serial dilutions skin prick tests (1/100-1/1.000.000) and serum allergen-specific IgG4 determinations were performed at baseline and at treatment conclusion. Results: Values on the scales suggested clinical improvement. There was a significant decrease in serial dilutions skin prick tests’ wheal diameters, as well as an increase in serum IgG4 values at treatment completion. IDIT was well tolerated. Conclusion:If the present results are confirmed by further studies, allergen-specific immunotherapy wider use could be promoted.

Melvin Kantono, Melvin Kantono, Beichu Guo et al.

Chronic Inflammation in tumor microenvironments is not only associated with various stages of tumor development, but also has significant impacts on tumor immunity and immunotherapy. Inflammasome are an important innate immune pathway critical for the production of active IL-1β and interleukin 18, as well as the induction of pyroptosis. Although extensive studies have demonstrated that inflammasomes play a vital role in infectious and autoimmune diseases, their role in tumor progression remains elusive. Multiple studies using a colitis-associated colon cancer model show that inflammasome components provide protection against the development of colon cancer. However, very recent studies demonstrate that inflammasomes promote tumor progression in skin and breast cancer. These results indicate that inflammasomes can promote and suppress tumor development depending on types of tumors, specific inflammasomes involved, and downstream effector molecules. The complicated role of inflammasomes raises new opportunities and challenges to manipulate inflammasome pathways in the treatment of cancer.

Fang Wang, Cun-yu Li, Yun-feng Zheng et al.

Reduning injection is a traditional Chinese medicine injection which has multiple functions such as clearing heat, dispelling wind, and detoxification. Although Reduning injection was widely utilized, reports of its allergenicity emerged one after another. However, there is little research on its allergenic substances. The aim of this study is to evaluate the sensitization of Reduning injection and explore the underlying cause of the anaphylactic reaction. The main ingredients in Reduning injection were analyzed before and after ultrafiltration. Ultrafiltrate Reduning injection, unfiltered Reduning injection, egg albumin, Tween-80, and nine effective components in Reduning injection were utilized to sensitize guinea pigs. The serum 5-hydroxytryptamine level was used to assess the sensitization effect of Reduning injection. We found a significant decrease in Tween-80 content comparing to other components in the injection after ultrafiltration. Unfiltered Reduning injection, Tween-80, chlorogenic acid, and cryptochlorogenin acid caused remarkable anaphylactoid reaction on guinea pigs while ultrafiltration Reduning resulted in a significantly lower degree of sensitization. Our results suggest that ultrafiltration could significantly reduce the sensitization of Reduning injection, which is likely due to the decrease of Tween-80. We also conjectured that the form of chlorogenic acid and cryptochlorogenin acid within the complex solution mixture may also affect the sensitizing effect.

A. Boos, B. Hagl, A. Schlesinger et al.

PLOS Pathogens Staff