RESUMEN
Schizophrenia, a multifaceted neuropsychiatric disorder characterized by disruptions in perception, cognition, and behavior, has been associated with neuroinflammatory processes. Emerging research has increasingly recognized the potential involvement of immune-related factors in the pathogenesis of schizophrenia, prompting investigations into biomarkers associated with inflammatory cascades. Among these biomarkers, Eosinophil Cationic Protein (ECP), traditionally known for its role in eosinophil-mediated immune responses, has garnered attention for its putative association with neuroinflammation in schizophrenia. This paper critically examines the current understanding of the role of ECP in schizophrenia. ECP, a cytotoxic protein released by eosinophils, has diverse immunomodulatory effects and has been identified in altered concentrations in individuals with schizophrenia. Studies have reported elevated levels of ECP in peripheral fluids of schizophrenia patients, suggesting a possible link between ECP dysregulation and the inflammatory milieu characteristic of the disorder. Moreover, the potential implications of ECP in neuroinflammatory processes relevant to schizophrenia pathophysiology are discussed. ECP's role in modulating immune responses and its potential impact on neuronal function, synaptic plasticity, and neurotoxicity within the central nervous system (CNS) are considered, highlighting the potential contribution of ECP to the neuroinflammatory mechanisms underlying schizophrenia. In conclusion, while the precise role of ECP in schizophrenia pathogenesis warrants further elucidation, exploring its association with neuroinflammation holds promise in unraveling new biomarkers and therapeutic avenues for managing this complex psychiatric disorder.
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Biomarcadores , Proteína Catiónica del Eosinófilo , Esquizofrenia , Humanos , Biomarcadores/metabolismo , Biomarcadores/sangre , Proteína Catiónica del Eosinófilo/metabolismo , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/metabolismo , Esquizofrenia/inmunología , Esquizofrenia/metabolismoAsunto(s)
Proteína Catiónica del Eosinófilo , Eosinofilia , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Síndrome de Hipersensibilidad a Medicamentos/sangre , Proteína Catiónica del Eosinófilo/sangre , Eosinofilia/inducido químicamente , Eosinofilia/diagnóstico , Exantema/inducido químicamente , Exantema/diagnósticoRESUMEN
BACKGROUND: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). AIM: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. METHODS: We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. RESULTS: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). CONCLUSIONS: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.
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Biomarcadores , Colitis Ulcerosa , Neurotoxina Derivada del Eosinófilo , Heces , Complejo de Antígeno L1 de Leucocito , Peroxidasa , Humanos , Biomarcadores/análisis , Biomarcadores/metabolismo , Femenino , Masculino , Heces/química , Adulto , Estudios Prospectivos , Complejo de Antígeno L1 de Leucocito/análisis , Persona de Mediana Edad , Peroxidasa/metabolismo , Colitis Ulcerosa/diagnóstico , Neurotoxina Derivada del Eosinófilo/análisis , Neurotoxina Derivada del Eosinófilo/metabolismo , Enfermedad de Crohn/diagnóstico , Proteína Catiónica del Eosinófilo/análisis , Proteína Catiónica del Eosinófilo/metabolismo , Adulto Joven , Enfermedades Inflamatorias del Intestino/diagnóstico , Estudios de Casos y Controles , Curva ROC , Progresión de la Enfermedad , Valor Predictivo de las PruebasRESUMEN
BACKGROUND/AIMS: Sensitization to staphylococcal superantigens (SAgs) could contribute to asthma severity. However, its relevance with eosinophilic phenotype has not yet been clarified. This study aimed to investigate associations between serum specific IgE levels to SAg and eosinophilic airway inflammation in adult asthmatics. METHODS: The serum specific IgE levels to 3 SAgs, including staphylococcal enterotoxin A (SEA) and B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured by ImmunoCAP in 230 adult asthmatic patients and 50 healthy controls (HCs). Clinical characteristics and laboratory parameters, including serum total/free IgE, and 2 eosinophil-activation markers, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), were analyzed according to blood eosinophil counts (BEC; 150 cells/µL) and serum specific IgE levels to 3 SAgs (0.35 kU/L). RESULTS: Asthmatic patients showed higher serum specific IgE levels to 3 SAgs than HCs (p < 0.05 for all). The serum total/clinfree IgE levels were significantly higher in asthmatics with positive IgE responses to 3 SAgs than those without (p < 0.05 for all). There were no significant differences in clinical parameters including age, asthma severity, comorbidities, or smoking according to IgE responses to 3 SAgs. Patients with positive IgE responses to SEB (not to SEA/TSST-1) had higher serum specific IgE levels to house dust mites and ECP/EDN as well as higher BEC with positive correlations between serum SEB-specific IgE levels and BEC/ECP/EDN (p < 0.05 for all). CONCLUSION: These findings suggest that serum SEB-specific IgE levels could contribute to eosinophil activation as well as IgE production in adult asthma.
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Asma , Enterotoxinas , Eosinófilos , Inmunoglobulina E , Fenotipo , Superantígenos , Humanos , Enterotoxinas/inmunología , Inmunoglobulina E/sangre , Masculino , Asma/inmunología , Asma/sangre , Asma/diagnóstico , Femenino , Persona de Mediana Edad , Adulto , Eosinófilos/inmunología , Estudios de Casos y Controles , Superantígenos/inmunología , Superantígenos/sangre , Biomarcadores/sangre , Anciano , Eosinofilia/inmunología , Eosinofilia/sangre , Eosinofilia/diagnóstico , Proteína Catiónica del Eosinófilo/sangre , Toxinas Bacterianas/inmunología , Toxinas Bacterianas/sangre , Neurotoxina Derivada del Eosinófilo/sangreRESUMEN
PURPOSE: Since its release, Dupilumab has shown great results in treating severe uncontrolled CRSwNP. However, there is a lack of real-world data beyond 12 months of follow-up, and it is not clear to what extent biomarkers are appropriate for monitoring and predicting the Dupilumab therapy success. Hence, this study aims to analyze biomarkers for monitoring therapy, predicting therapy success and assess the effect of Dupilumab in real-world settings. METHODS: The follow-up was performed with 104 patients retrospectively up to 22 months, assessing SNOT-22, NPS, olfactometry, ACS, FEV-1, and blood biomarkers (total serum IgE, Eosinophils, ECP). Patients were divided into subgroups depending on their pretherapeutic biomarker levels and subsequent development was analyzed. RESULTS: There was substantially improvement in all clinical parameters up to 1 year and then continuously up to month 22. Patients with initially elevated baseline blood eosinophil counts (> 0.5 billion/L) had a trend of better SNOT-22 development after 1 year (- 12.19 points, p = 0.03). The course of total serum IgE showed moderate correlation with almost all clinical variables obtained. Therapy was well tolerated with only mild and transient adverse events. CONCLUSION: Dupilumab has considerably reduced symptoms and disease severity even beyond 1 year of treatment, supporting its role as targeted and effective treatment option for CRSwNP. Our data shows that total serum IgE is a promising biomarker for the monitoring during the treatment with Dupilumab. Elevated pre-therapeutic serum eosinophil counts may be a predictor of good subjective response to therapy. Larger cohorts and a long-term-follow-up over years are needed to further consolidate these findings.
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Anticuerpos Monoclonales Humanizados , Biomarcadores , Inmunoglobulina E , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Biomarcadores/sangre , Estudios de Seguimiento , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Inmunoglobulina E/sangre , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/sangre , Eosinófilos , Sinusitis/tratamiento farmacológico , Sinusitis/sangre , Rinitis/tratamiento farmacológico , Rinitis/sangre , Enfermedad Crónica , Resultado del Tratamiento , Proteína Catiónica del Eosinófilo/sangre , AncianoRESUMEN
OBJECTIVES: Inflammatory bowel disease (IBD), eosinophilic gastrointestinal disease (EGID), and functional abdominal pain disorder (FAPD) present with nonspecific gastrointestinal (GI) symptoms clinically and also have some similarities in pathogeneses associated with eosinophils. Therefore, we aimed to evaluate the role of eosinophils in IBD compared to EGID and FAPD by investigating eosinophils in peripheral blood and GI tissue and eosinophil cationic protein (ECP). METHODS: Pediatric patients with chronic GI symptoms who underwent endoscopic biopsies were enrolled. Complete blood cell counts, inflammatory markers, immunoglobulin E (IgE), serum ECP levels, and endoscopic and histopathologic findings were retrospectively reviewed. RESULTS: A total of 387 patients were included: 179 with EGID, 107 with IBDs, and 82 with FAPD. Peripheral absolute eosinophil count (AEC), total IgE, and serum ECP were significantly higher in both IBD and EGID than in FAPD (all p < 0.05). Statistically significant differences were noted among the three groups in tissue eosinophil counts in each segment of GI tract except for the esophagus (p < 0.05). Significant differences were observed in tissue eosinophil counts in the ascending, sigmoid colon, and rectum between EGID and IBD (p < 0.05). Peripheral and tissue eosinophils in the stomach and duodenum revealed positive correlation in both EGID and IBD (both p < 0.001). CONCLUSION: Elevated eosinophil-related markers, as well as increased tissue eosinophilic infiltration in the affected areas of the GI tract in both IBD and EGID compared to FAPD, suggest that eosinophils might play a common important role in the pathogeneses of both diseases.
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Enteritis , Eosinofilia , Eosinófilos , Gastritis , Enfermedades Inflamatorias del Intestino , Humanos , Niño , Eosinófilos/patología , Proteína Catiónica del Eosinófilo , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/patología , Inmunoglobulina E , Recuento de LeucocitosRESUMEN
BACKGROUND: Serum eosinophil cationic protein (ECP) levels affect the surgical outcome of chronic rhinosinusitis (CRS) with nasal polyps. Primary CRS can be classified into type 2 (T2) and non-T2. We aimed to differentiate the role of serum ECP levels in surgical outcomes between the distinct endotypes of primary CRS. METHODS: We prospectively enrolled patients with bilateral primary CRS who underwent surgical treatment with postoperative follow-up for at least 12 months. Endotyping and serum parameter measurements were completed within 1 week before surgery. RESULTS: In total, 113 patients were enrolled, including 65 with T2 CRS and 48 with non-T2 CRS. Patients in the T2 CRS group with uncontrolled CRS had significantly higher serum ECP levels than those in patients in the non-T2 CRS group. An optimal cut-off value was obtained at 17.0 λg/L using the receiver operating characteristic curve, attaining a sensitivity of 91.7% and specificity of 56.6%. Multivariate logistic regression analysis showed that a higher serum ECP level was an independent factor for postoperative uncontrolled disease. The hazard ratio was 11.3 for the T2 group, with serum ECP levels over 17.0 λg/L. In the non-T2 group, no parameters were significantly correlated with postoperative uncontrolled CRS. CONCLUSIONS: Serum ECP levels appear to be a feasible predictor of postoperative uncontrolled disease in patients with T2 CRS as preoperative serum ECP levels >17.0 λg/L in these patients have an approximately 16.7-fold increased risk of postoperative uncontrolled disease and should be closely monitored.
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Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Humanos , Proteína Catiónica del Eosinófilo , Rinitis/etiología , Enfermedad Crónica , Sinusitis/complicaciones , Pólipos Nasales/complicaciones , Pólipos Nasales/cirugía , EosinófilosRESUMEN
BACKGROUND: Individuals genetically susceptible to high schistosomiasis worm burden may contribute disproportionately to transmission and could be prioritized for control. Identifying genes involved may guide development of therapy. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 606 children aged 10-15 years were recruited in the Albert Nile region of Uganda and assessed for Schistosoma mansoni worm burden using the Up-Converting Particle Lateral Flow (UCP-LF) test detecting circulating anodic antigen (CAA), point-of-care Circulating Cathodic Antigen (POC-CCA) and Kato-Katz tests. Whole genome genotyping was conducted on 326 children comprising the top and bottom 25% of worm burden. Linear models were fitted to identify variants associated with worm burden in preselected candidate genes. Expression quantitative trait locus (eQTL) analysis was conducted for candidate genes with UCP-LF worm burden included as a covariate. Single Nucleotide Polymorphism loci associated with UCP-LF CAA included IL6 rs2066992 (OR = 0.43, p = 0.0006) and rs7793163 (OR = 2.0, p = 0.0007); IL21 SNP kgp513476 (OR 1.79, p = 0.0025) and IL17B SNP kgp708159 (OR = 0.35, p = 0.0028). A haplotype in the IL10 locus was associated with lower worm burden (OR = 0.53, p = 0.015) and overlapped SNPs rs1800896, rs1800871 and rs1800872. Significant haplotypes (p<0.05, overlapping significant SNP) associated with worm burden were observed in IL6 and the Th17 pathway IL12B and IL17B genes. There were significant eQTL in the IL6, IL5, IL21, IL25 and IFNG regions. CONCLUSIONS: Variants associated with S. mansoni worm burden were in IL6, FCN2, RNASE3, IL10, IL12B and IL17B gene loci. However only eQTL associations remained significant after Bonferroni correction. In summary, immune balance, pathogen recognition and Th17 pathways may play a role in modulating Schistosoma worm burden. Individuals carrying risk variants may be targeted first in allocation of control efforts to reduce the burden of schistosomiasis in the community.
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Esquistosomiasis mansoni , Esquistosomiasis , Adolescente , Animales , Niño , Humanos , Antígenos Helmínticos , Proteína Catiónica del Eosinófilo , Heces/química , Interleucina-10 , Subunidad p40 de la Interleucina-12 , Interleucina-6/genética , Schistosoma mansoni/genética , Esquistosomiasis/diagnóstico , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/diagnóstico , Sensibilidad y Especificidad , Uganda/epidemiologíaRESUMEN
OBJECTIVE: In a previous study, we reported an increase of nasal nerve growth factor (NGF) in patients treated with high-pressure administration of sterile saline isotonic solution (HPpSIS). Herein we characterized the nasal mucosa in terms of innate immune response and cytokine signature, including antiviral properties. Potential NGF and antiviral benefits of HPpSIS were also discussed. PATIENTS AND METHODS: Twenty (20) patients (11 males, 9 females; age range 30-75 years old) underwent HPpSIS and nasal samples were collected before and after treatment. Nasal scraping was used for morphological (smears and Quick May-Grunwald Giemsa staining, MGG), biochemical (Histamine, Serotonin; ELISA) and molecular (messenger RNA, mRNA) analyses. Amplification of transcripts specific for Toll-like receptor (TLR) 3 (TLR3), TLR7, TLR9, Interleukin-(IL) 18 (IL18), IL13, IL12, eosinophil-derived neurotoxin (EDN), Eosinophil Cationic Protein (ECP), γ Interferon (γIFN), tryptase and serotonin was performed using the 2-step real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR). Clinical and laboratory data were analyzed and compared. RESULTS: The clinical evaluation showed a protective effect of our therapy. Smears showed the presence of leucocytes, eosinophils (EOs) and mast cells (MCs), and increased immunoreactivity for ECP/RNase3 and EDN after HPpSIS. ELISA showed increased levels of Serotonin and EDN associated with unchanged levels of substance P(SP) and histamine. Increased eosinophil-derived neurotoxin eosinophil-derived neurotoxin (EDN) levels were confirmed by in situ fluorescent analysis. HPpSIS induced the upregulation of TLR3, TLR7 and TLR9 transcripts, while no changes were observed for Intercellular Adhesion Molecule 1 (ICAM1), IL18, Interleukin-15 (IL15) and IL12 transcripts nor for Interleukin-6 (IL6) and IL13. No changes were also observed for γIFN and EDN/RNase2 transcripts, while ECP/RNase3 transcripts were significantly upregulated after HPpSIS. Finally, tryptase transcripts were unchanged while serotonin transcripts were significantly increased after HPpSIS. CONCLUSIONS: The clinical and biomolecular changes observed at the nasal mucosa due to HpSS treatment suggest the activation of an innate surveillance, by means of TLR transcription, and a possible anti-viral response due to EDN upregulation. It remains to be verified if NGF, known to be released locally upon HpSIS treatment, might in part be responsible for this local activation.
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Interleucina-18 , Receptor Toll-Like 3 , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Neurotoxina Derivada del Eosinófilo/genética , Neurotoxina Derivada del Eosinófilo/metabolismo , Interleucina-18/metabolismo , Receptor Toll-Like 3/metabolismo , Triptasas , Factor de Crecimiento Nervioso/metabolismo , Receptor Toll-Like 7/genética , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Histamina/metabolismo , Interleucina-13 , Serotonina/metabolismo , Proteína Catiónica del Eosinófilo/metabolismo , Eosinófilos , Antivirales/farmacología , Antivirales/metabolismo , Interleucina-12/metabolismoRESUMEN
Several pieces of evidence point to an allergic component as a trigger of acute appendicitis. As the Th2 immune response is characterized by eosinophil mobilization to the target organ and release of their cationic granule proteins, it is reasonable to investigate if the degranulation of eosinophils could be associated with the local injury. The primary aim of this study is to evaluate the participation of eosinophils granules proteins in acute appendicitis, both at local and systemic levels and the secondary aim is to evaluate the diagnostic accuracy of eosinophils granules proteins for the detection of acute appendicitis, as well as for distinguishing between complicated and uncomplicated acute appendicitis. Eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and eosinophil peroxidase (EP) are the most well-known eosinophil granule proteins. From August 2021 to April 2022, we present a prospective single-center study to evaluate the EDN, ECP, and EP concentrations simultaneously in appendicular lavage fluid (ALF) and the serum of 22 patients with acute phlegmonous appendicitis (APA), 24 with acute gangrenous appendicitis (AGA), and 14 normal controls. Concerning EDN, no differences were found between groups. ECP concentrations in ALF and serum were significantly higher in the histologically confirmed acute appendicitis compared to the control groups (p < 0.0001 and p < 0.0001, respectively). In ALF, no differences were found between ECP levels in APA: 38.85 ng/mL (IQR 26.50-51.77) and AGA 51.55 ng/mL (IQR 39.55-70.09) groups (p = 0.176). In the serum, no difference was found between ECP levels at APA: 39 ng/mL (IQR 21.30-56.90) and AGA: 51.30 ng/mL (IQR 20.25-62.59) (p = 0.100). For EP, the concentrations in ALF (p < 0.001) and serum (p < 0.001) were both higher in acute appendicitis compared to the control. In ALF, no difference was found between APA: 240.28 ng/mL (IQR 191.2-341.3) and AGA: 302.5 (IQR 227.7-535.85) (p = 0.236). In the serum, no differences were found between APA: 158.4 ng/mL (IQR 111.09-222.1) and AGA: 235.27 (IQR 192.33-262.51) (p = 0.179). Globally, the ALF concentrations were higher than serum concentrations, reflecting an intense inflammatory local reaction in AA. The optimal ECP cut-off for discriminating between acute appendicitis and the controls was >11.41 ng/mL, with a sensitivity of 93.5%, but with a specificity for identifying appendicitis of 21.4%, good discriminative power (AUC = 0.880). For EP, the optimal cut-off was >93.20 ng/mL, with a sensitivity of 87%, but with a specificity of 14.3% (AUC = 0.901), excellent discriminative power. For the diagnosis of perforated AA, the discriminative power of ECP and EP serum concentrations are weak (AUC = 0.562 and AUC = 0.664, respectively). Concerning the presence of peritonitis, the discriminative power of ECP and EP serum concentrations is acceptable, respectively: AUC = 0.724 and AUC = 0.735. Serum levels of EDN (p = 0.119), ECP (p = 0.586) and EP (p = 0.08) in complicated appendicitis were similar to uncomplicated appendicitis. Serum concentrations of ECP and EP can be added to decision-making AA diagnosis. A Th2-type immune response is present in AA. These data bring forward the role of an allergic reaction in the pathogenesis of acute appendicitis.
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Apendicitis , Humanos , Proteínas en los Gránulos del Eosinófilo/metabolismo , Apendicitis/diagnóstico , Apendicitis/metabolismo , Apendicitis/patología , Estudios Prospectivos , Proteínas Sanguíneas/metabolismo , Ribonucleasas/metabolismo , Eosinófilos/metabolismo , Neurotoxina Derivada del Eosinófilo/metabolismo , Proteína Catiónica del Eosinófilo/metabolismo , Enfermedad AgudaRESUMEN
OBJECTIVES: To investigate the value of secretions Eosinophilic cationic protein (ECP) detection in the diagnosis of endotypes of Chronic rhinosinusitis (CRS) and its correlation with clinical symptoms, so as to provide guidance for the clinical application of EOS and ECP detection in secretions. METHODS: Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their EOS% and ECP levels were measured. Correlation analysis was performed for EOS% and ECP levels in secretions and tissues, respectively. The correlation between secretions EOS% and ECP and clinical symptom scores (symptomatic visual analog scale (VAS) scores, Lanza-kennedy scores from nasal endoscopy and Lund-Mackay scores from sinus CT) was further analyzed. Receiver operating characteristic curves were used to assess the predictive potential of EOS% and ECP in nasal secretions. RESULTS: Eosinophilic chronic rhinosinusitis (ECRS) patients had higher concentrations of ECP in nasal secretions than healthy subjects and NECRS (non-eosinophilic CRS) (p < 0.0001;0.0001); EOS% in nasal secretions was higher in ECRS than healthy subjects (p = 0.0055), but the differences between ECRS and NECRS were not statistically significant (p = 0.0999). Correlation analysis showed that tissue EOS% was correlated with ECP concentration and EOS% in nasal secretions (R = 0.5943;0.2815). There was a correlation between EOS% in secretions with a total LM score (R = 0.3131); ECP concentration in secretions with a total LK score (R = 0.3792). To diagnose ECRS, the highest area under the curve (0.8230) was determined for ECP in secretions; the highest area under the curve (0.6635) was determined for EOS% in secretions. CONCLUSION: Measurement of ECP in nasal secretions is useful for non-invasive diagnosis of ECRS. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3304-3312, 2023.
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Eosinofilia , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Rinitis/diagnóstico , Rinitis/metabolismo , Proteína Catiónica del Eosinófilo , Eosinofilia/diagnóstico , Pólipos Nasales/diagnóstico , Pólipos Nasales/metabolismo , Sinusitis/diagnóstico , Sinusitis/metabolismo , Enfermedad Crónica , EosinófilosRESUMEN
OBJECTIVES: To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions. METHODS: We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions. RESULTS: Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions. CONCLUSIONS: Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.
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Pólipos Nasales , Rinitis , Sinusitis , Humanos , Rinitis/diagnóstico , Rinitis/metabolismo , Proteína Catiónica del Eosinófilo/metabolismo , Peroxidasa , Enfermedad Crónica , Sinusitis/diagnóstico , Sinusitis/metabolismo , Biomarcadores , Pólipos Nasales/diagnóstico , Pólipos Nasales/metabolismoRESUMEN
The evolutionary role of conformational exchange in the emergence and preservation of function within structural homologs remains elusive. While protein engineering has revealed the importance of flexibility in function, productive modulation of atomic-scale dynamics has only been achieved on a finite number of distinct folds. Allosteric control of unique members within dynamically diverse structural families requires a better appreciation of exchange phenomena. Here, we examined the functional and structural role of conformational exchange within eosinophil-associated ribonucleases. Biological and catalytic activity of various EARs was performed in parallel to mapping their conformational behavior on multiple timescales using NMR and computational analyses. Despite functional conservation and conformational seclusion to a specific domain, we show that EARs can display similar or distinct motional profiles, implying divergence rather than conservation of flexibility. Comparing progressively more distant enzymes should unravel how this subfamily has evolved new functions and/or altered their behavior at the molecular level.
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Proteína Catiónica del Eosinófilo , Ribonucleasas , Humanos , Conformación Proteica , Eosinófilos , Espectroscopía de Resonancia Magnética , Resonancia Magnética Nuclear BiomolecularRESUMEN
Background: Neutrophils are involved in the pathophysiology of allergic asthma, where the Eosinophil Cationic Protein (ECP) is a critical inflammatory mediator. Although ECP production is attributed to eosinophils, we reported that ECP is also present in neutrophils from allergic patients where, in contrast to eosinophils, it is produced in an IgE-dependent manner. Given the key role of ECP in asthma, we investigated the molecular mechanisms involved in ECP production as well as the effects induced by agonists and widely used clinical approaches. We also analyzed the correlation between ECP production and lung function. Methods: Neutrophils from allergic asthmatic patients were challenged with allergens, alone or in combination with cytokines, in the presence of cell-signaling inhibitors and clinical drugs. We analyzed ECP levels by ELISA and confocal microscopy. Lung function was assessed by spirometry. Results: IgE-mediated ECP release is dependent on phosphoinositide 3-kinase, the extracellular signal-regulated kinase (ERK1/2) and the production of reactive oxygen species by NADPH-oxidase. Calcineurin phosphatase and the transcription factor NFAT are also involved. ECP release is enhanced by the cytokines interleukin (IL)-5 and granulocyte macrophage-colony stimulating factor, and inhibited by interferon-γ, IL-10, clinical drugs (formoterol, tiotropium and budesonide) and allergen-specific IT. We also found an inverse correlation between asthma severity and ECP levels. Conclusions: Our results suggest the molecular pathways involved in ECP production and potential therapeutic targets. We also provide a new method to evaluate disease severity in asthmatic patients based on the quantification of in vitro ECP production by peripheral neutrophils.
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Asma , Hipersensibilidad , Humanos , Proteína Catiónica del Eosinófilo/metabolismo , Neutrófilos/metabolismo , Fosfatidilinositol 3-Quinasas , Alérgenos , Asma/tratamiento farmacológico , Asma/metabolismo , Citocinas/metabolismo , Inmunoglobulina ERESUMEN
Objective: This study aimed to clarify the characteristics of cough-reflex sensitivity and airway inflammation in patients with sinobronchial syndrome (SBS). Methods: 39 patients with SBS, 53 patients with upper airway cough syndrome (UACS) induced by rhinitis, 33 patients with chronic sinusitis without cough, and 39 healthy controls (HCs) were enrolled between January 2013 and December 2018. All participants underwent a capsaicin cough-sensitivity test and cytology of induced sputum. The concentration of calcitonin-gene-related peptide (CGPR), histamine, prostaglandin (PG) E2, and eosinophil cationic protein (ECP) in induced sputum were measured using enzyme-linked immunosorbent assays (ELISAs). Results: The lowest concentration of capsaicin solution that induced ≥5 coughs (C5) was decreased markedly in patients with UACS induced by rhinitis compared with SBS patients (1.95 ± 2.92 vs. 31.2 ± 58.6 mol/L, P < 0.001), indicating higher cough-reflex sensitivity among UACS patients induced by rhinitis. However, there was no difference of these threshold between SBS patients and patients with sinusitis without cough and HCs. The percentage of neutrophils in sputum was increased remarkably in patients with SBS compared with HCs (40.0 ± 48.5% vs. 5.5 ± 9.0%, P < 0.001). A higher concentration of CGPR, histamine, and PGE2 was observed in induced sputum from patients with UACS induced by rhinitis than that in controls, and the ECP level was increased significantly in UACS induced by rhinitis compared with that in the other three groups. Conclusions: Cough-reflex sensitivity and airway inflammation in patients with SBS were different in patients with UACS induced by rhinitis. Thus, the mechanism of cough in those two patient populations might differ. Our study is registered in the Chinese Clinical Trials Register (https://www.chictr.org.cn/) as ChiCTR-TRC-00000152.
Asunto(s)
Rinitis , Sinusitis , Humanos , Capsaicina/efectos adversos , Tos , Dinoprostona/análisis , Proteína Catiónica del Eosinófilo , Histamina/análisis , Inflamación , Rinitis/complicaciones , Sinusitis/complicaciones , Péptido Relacionado con Gen de Calcitonina/análisisRESUMEN
INTRODUCTION: Allergic sensitization is an important factor in the development, severity, and exacerbation of asthma, which is attributed to type 2 (T2) inflammation. Evidence suggests that respiratory bacterial pathogens (e.g., Streptococcus pneumoniae) exert suppressive effects on airway T2 inflammation. To clarify the role of allergic inflammation in bacterial colonization in asthma based on allergic sensitization, we investigated pharyngeal bacterial colonization, biomarkers (e.g., serum eosinophil cationic protein (ECP) and cytokines/chemokines), and symptoms in the acute exacerbation of childhood asthma. METHODS: Pharyngeal samples were collected from 53 children (mean/median age 2.7/2.5 years). Serum levels of total and allergen-specific IgE against aeroallergens, ECP, and 17 cytokines/chemokines were measured. RESULTS: Allergic sensitization was recognized in 62.2% patients. S. pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and other bacteria were detected in 47.1%, 11.3%, 11.3%, and 30.1% of all patients, respectively. Patients with S. pneumoniae had a significantly shorter duration of wheezing than those without (4.7 ± 3.6 vs. 7.1 ± 3.5 days, p = 0.024). In patients with allergic sensitization, patients with S. pneumoniae had a significantly shorter duration of wheezing than those without (4.0 ± 3.6 vs. 7.7 ± 4.0 days, p = 0.003). Serum total IgE was significantly lower in patients with S. pneumoniae than in those without (81.9 [7.8-894] vs. 287 [4.4-1,840] IU/mL, p = 0.014). Serum ECP was significantly higher (33.1 [2-109] vs. 7.8 [3-35] ng/mL, p = 0.042), and IFN-γ was significantly lower (5.6 [4-10] vs. 16.4 [7-28] pg/mL, p = 0.032) in patients with allergic sensitization than those without. DISCUSSION/CONCLUSION: Our results suggested that the suppressive effects of S. pneumoniae colonization were observed only in patients with allergic sensitization, wherein serum total IgE, ECP, and IFN-γ may have an important role on acute exacerbation of asthma.
Asunto(s)
Asma , Streptococcus pneumoniae , Niño , Humanos , Preescolar , Ruidos Respiratorios , Asma/diagnóstico , Inmunoglobulina E , Proteína Catiónica del Eosinófilo , Citocinas , Quimiocinas , InflamaciónRESUMEN
BACKGROUND: Leptospirosis is an emerging zoonotic infection worldwide and a cause of life-threatening disease in dogs. Seroprevalence in Swedish dogs is unknown. The aims of the present study were to estimate seroprevalence of pathogenic Leptospira in healthy dogs in Sweden using the microagglutination test (MAT) and a rapid point-of-care enzyme-linked immunosorbent assay (ELISA), and to evaluate risk factors of Leptospira exposure in Swedish dogs. RESULTS: Positive MAT titres (≥ 1:50) were detected in 27/369 (7.3%) of included dogs. Five different serovars were represented of which the Saxkoebing serovar was the most common (64.3%), followed by Copenhagi (14.3%), Bratislava (10.7%), Icterohaemorrhagiae (7.1%), and Canicola (3.6%). The ELISA test (SNAP® Lepto) was positive in 3/316 (0.9%) dogs. Living in urban areas and contact with stagnant water were found to be risk factors for Leptospira seropositivity (p < 0.05) in a multivariable logistic regression model. CONCLUSION: In this first seroprevalence study of Leptospira in Swedish dogs, it was shown that healthy dogs without recent (24 months) travel history and antileptospira vaccination had been exposed to pathogenic Leptospira interrogans serovars. Contact with stagnant water and living in urban areas were independent risk factors for seropositivity.
Asunto(s)
Enfermedades de los Perros , Leptospira , Leptospirosis , Perros , Animales , Estudios Seroepidemiológicos , Suecia/epidemiología , Proteína Catiónica del Eosinófilo , Anticuerpos Antibacterianos , Enfermedades de los Perros/epidemiología , Leptospirosis/epidemiología , Leptospirosis/veterinaria , Factores de Riesgo , AguaRESUMEN
Objectives: The gut microbiota and its metabolites are linked to inflammation and contribute to the progression of atrial fibrillation (AF), but the predictive value of the gut microbiota-derived metabolite lipopolysaccharide (LPS) for AF recurrence (RAF) is unknown. This study is aimed at investigating (1) the correlation between LPS and RAF and (2) its relationship with inflammation and atrial fibrosis. Method: We performed a single-centre retrospective analysis in 159 AF patients. Fasting plasma samples were collected, and an enzyme-linked immunosorbent assay was used to determine the levels of serum LPS, interleukin-6 (IL-6), collagen type-1 C-terminal telopeptide (CITP), and transforming growth factor-ß1 (TGFß1). The cumulative risk for RAF was evaluated with Kaplan-Meier analysis. Cox proportional hazard analysis was carried out to predict the hazard of RAF. The correlations among LPS and IL-6, CITP, TGFß1, and left atrial diameter (LAD) were analysed by Pearson's correlation coefficient. Subsequent univariate and multivariable linear regression analyses were carried out to evaluate the connection between clinical variables and Log-LPS. Results: All 159 AF patients were included in this study. The proportion of persistent atrial fibrillation was 40.3%, the mean age was 61.9 ± 10.1 years, the proportion of males was 61.6%, and the mean LPS was 56.5 ± 29.5 pg/mL. After all patients were divided into tertiles according to the circulating LPS level, a total of 44 RAF occurred: 10 in the first tertile, 15 in the second tertile, and 19 in the third tertile (log-rank test P = 0.037). Heart failure (hazard ratio 2.029, P = 0.041), LAD (hazard ratio 1.064, P = 0.022), Log-LPS (hazard ratio 5.686, P = 0.043), and CITP (hazard ratio 6.841, P = 0.033) independently predicted the risk of RAF. In all patients, univariate analysis showed that heart failure, LAD, hs-CRP, IL-6, CITP, and TGF-ß1 were connected with Log-LPS. Multivariate linear regression analysis indicated that IL-6 and hs-CRP were independently and positively connected with Log-LPS. Conclusions: Our results indicated that circulating LPS was a predictor of RAF and may contribute to RAF incidence after ablation by increasing systemic inflammation and atrial fibrosis.