RESUMO
OBJECTIVE: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. METHODS: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. RESULTS: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. CONCLUSION: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.
Assuntos
Resistência a Medicamentos , Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Lactente , China , Receptores de Interleucina-2/sangue , Criança , Valor Preditivo dos Testes , População do Leste AsiáticoRESUMO
We developed a highly sensitive assay for detecting protein-protein interaction using chimeric receptors comprising two molecules of interest in the extracellular domain and interferon alpha and beta receptor subunit 1 or 2 (IFNAR1/2) in the intracellular domain. This intracellular IFNAR1/2 reconstitution system (IFNARRS) proved markedly more sensitive than the NanoBiT system, currently considered one of the best detection systems for protein interaction. Employing chimeric receptors with extracellular domains from the IFNγ or IL-2 receptor and the intracellular domains of IFNAR1/2, the IFNARRS system effectively identifies low IFNγ or IL-2 levels. Cells stably expressing these chimeric receptors responded to IFNγ secreted by activated T cells following various stimuli, including a specific peptide-antigen. The activation signals were further enhanced by the expression of relevant genes, such as costimulators, via IFN-stimulated response elements in the promoters. Besides IFNγ or IL-2, the IFNARRS system demonstrated the capability to detect other cytokines by using the corresponding extracellular domains from these target cytokine receptors.
Assuntos
Interferon gama , Interleucina-2 , Receptor de Interferon alfa e beta , Linfócitos T , Humanos , Receptor de Interferon alfa e beta/metabolismo , Receptor de Interferon alfa e beta/genética , Linfócitos T/metabolismo , Linfócitos T/imunologia , Interleucina-2/metabolismo , Interferon gama/metabolismo , Receptores de Interleucina-2/metabolismo , Receptores de Interleucina-2/genética , Ligação Proteica , Ativação Linfocitária , Células HEK293RESUMO
Neurosarcoidosis, a rare granulomatous disease, causes inflammation and damage to the central nervous system (CNS). A major diagnostic challenge in neurosarcoidosis is the absence of well-defined biomarkers. The need for biopsy to make the diagnosis can lead to delays and misdiagnosis if histopathology is inaccessible or indeterminate, highlighting the need for more accessible diagnostic indicators. The current gold standard for a "definite" neurosarcoidosis diagnosis requires biopsy of CNS tissue revealing non-caseating granulomas. However, such biopsies are inherently invasive and carry associated procedural risks. Notably, angiotensin-converting enzyme (ACE), commonly associated with systemic sarcoidosis, is recognized as a poor biomarker for neurosarcoidosis due to its lack of accuracy in the context of CNS involvement. Furthermore, imaging in neurosarcoidosis, while widely utilized and important for narrowing the diagnosis, lacks specificity. Decades of research have yielded molecular and immunologic biomarkers-soluble interleukin-2 receptor (IL-2R), serum amyloid A1, the CD4/CD8 ratio, neopterin, interferon-gamma (IFN-γ), and chemokine ligand 2 (CCL2)-that hold potential for improving diagnostic accuracy. However, these biomarkers are not yet established in clinical care as they may be difficult to obtain and are derived from small studies. They also suffer from a lack of specificity against other inflammatory and infectious central nervous system diseases. New biomarkers are needed for use alongside those previously discovered to improve diagnosis of this rare disease. This review synthesizes existing literature on neurosarcoidosis biomarkers, aiming to establish a foundation for further research in this evolving field. It also consolidates information on biomarkers of systemic sarcoidosis such as IL-8 and soluble CD40L that have not yet been studied in neurosarcoidosis but hold potential as markers of CNS disease.
Assuntos
Biomarcadores , Doenças do Sistema Nervoso Central , Sarcoidose , Sarcoidose/líquido cefalorraquidiano , Sarcoidose/diagnóstico , Sarcoidose/sangue , Humanos , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/sangue , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/sangue , Biópsia , Peptidil Dipeptidase A/líquido cefalorraquidiano , Peptidil Dipeptidase A/sangue , Receptores de Interleucina-2/sangueRESUMO
Nuclear factor Foxp3 determines regulatory T (Treg) cell fate and function via mechanisms that remain unclear. Here, we investigate the nature of Foxp3-mediated gene regulation in suppressing autoimmunity and antitumor immune response. Contrasting with previous models, we find that Foxp3-chromatin binding is regulated by Treg activation states, tumor microenvironment, and antigen and cytokine stimulations. Proteomics studies uncover dynamic proteins within Foxp3 proximity upon TCR or IL-2 receptor signaling in vitro, reflecting intricate interactions among Foxp3, signal transducers, and chromatin. Pharmacological inhibition and genetic knockdown experiments indicate that NFAT and AP-1 protein Batf are required for enhanced Foxp3-chromatin binding in activated Treg cells and tumor-infiltrating Treg cells to modulate target gene expression. Furthermore, mutations at the Foxp3 DNA-binding domain destabilize the Foxp3-chromatin association. These representative settings delineate context-dependent Foxp3-chromatin interaction, suggesting that Foxp3 associates with chromatin by hijacking DNA-binding proteins resulting from Treg activation or differentiation, which is stabilized by direct Foxp3-DNA binding, to dynamically regulate Treg cell function according to immunological contexts.
Assuntos
Cromatina , Fatores de Transcrição Forkhead , Linfócitos T Reguladores , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Cromatina/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Transdução de Sinais , Ligação Proteica , Humanos , Regulação da Expressão Gênica , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Interleucina-2/metabolismo , Receptores de Interleucina-2/genética , Diferenciação CelularRESUMO
BACKGROUND AND AIMS: The majority of indeterminate pediatric acute liver failure (PALF) cases are secondary to immune dysregulation, labeled activated T-cell hepatitis (TCHep). We aimed to describe a cohort of children with acute severe hepatitis and PALF and define how clinical immune labs may help identify the TCHep group. METHODS: Retrospective review of children with acute hepatitis and PALF between March 2020 and August 2022. Patients were classified as known diagnosis, indeterminate hepatitis (IND-Hep), or TCHep (defined by liver biopsy with predominant CD8 T-cell inflammation or development of aplastic anemia). RESULTS: 124 patients were identified: 83 with known diagnoses, 16 with TCHep, and 25 with IND-Hep. Patients with TCHep had significantly increased median total bilirubin levels (7.5 mg/dL (IQR 6.8-8.9) vs 1.5 mg/dL (IQR 1.0-3.6), p < 0.0001), soluble interleukin-2 receptor levels (4512 IU/mL (IQR 4073-5771) vs 2997 IU/mL (IQR 1957-3237), p = 0.02), and percent of CD8+ T-cells expressing perforin (14.5 % (IQR 8.0-20.0) vs 1.0 % (IQR 0.8-1.0), p = 0.004) and granzyme (37.5 % (IQR 15.8-54.8) vs 4.0 % (IQR 2.5-5.5), p = 0.004) compared to IND-Hep patients. Clinical flow cytometry showed that TCHep patients had significantly increased percent CD8+ T cells (29.0 % (IQR 24.5-33.5) vs 23.6 % (IQR 19.8-25.8), p = 0.04) and HLA-DR+ (16.0 % (IQR 14.5-24.5) vs 2.7 (1.8-5.3), p < 0.001) compared to IND-Hep patients indicative of increase in CD8+ T cells that are activated. CONCLUSIONS: Peripheral blood clinical immune studies demonstrate increased markers of CD8 T-cell activation, proliferation, and cytotoxic function for TCHep patients. These readily available immune function labs can be used to help distinguish patients with TCHep from those with other causes. This provides a non-invasive tool for early detection of potential TCHep before progression to liver failure.
Assuntos
Linfócitos T CD8-Positivos , Humanos , Estudos Retrospectivos , Criança , Masculino , Feminino , Pré-Escolar , Linfócitos T CD8-Positivos/imunologia , Falência Hepática Aguda/imunologia , Falência Hepática Aguda/sangue , Adolescente , Hepatite/imunologia , Hepatite/sangue , Ativação Linfocitária , Lactente , Receptores de Interleucina-2/sangue , Granzimas/sangueRESUMO
BACKGROUND: The aim of this study was to establish features of inflammation in histologically normal gallbladders with gallstones and compare the expression of inflammatory markers in acutely and chronically inflamed gallbladders. METHODS: Immunohistochemistry was performed on formalin-fixed paraffin-embedded gallbladders for tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-2R, and substance p in three groups: Group I (n = 60) chronic cholecystitis, Group II (n = 57) acute cholecystitis and Group III (n = 45) histologically normal gallbladders with gallstones. Expression was quantified using the H-scoring system. RESULTS: Median, interquartile range expression of mucosal IL-2R in Groups I (2.65, 0.87-7.97) and II (12.30, 6.15-25.55) was significantly increased compared with group III (0.40, 0.10-1.35, p < 0.05). Submucosal IL-2R expression in Groups I (2.0, 1.12-4.95) and II (10.0, 5.95-14.30) was also significantly increased compared with Group III (0.50, 0.15-1.05, p < 0.05). There was no difference in the lymphoid cell IL-6 expression between Groups I (5.95, 1.60-18.15), II (6.10, 1.1-36.15) and III (8.30, 2.60-26.35, p > 0.05). Epithelial IL-6 expression of Group III (8.3, 2.6-26.3) was significantly increased compared with group I (0.5, 0-10.2, p < 0.05) as was epithelial TNF-α expression in Group III (85.0, 70.50-92.0) compared with Groups I (72.50, 45.25.0-85.50, p < 0.05) and II (61.0, 30.0-92.0, p < 0.05). Lymphoid cell Substance P expression in Groups I (1.90, 1.32-2.65) and II (5.62, 2.50-20.8) was significantly increased compared with Group III (1.0,1.0-1.30, p < 0.05). Epithelial cell expression of Substance P in Group III (121.7, 94.6-167.8) was significantly increased compared with Groups I (75.7, 50.6-105.3, p < 0.05) and II (78.9, 43.5-118.5, p < 0.05). CONCLUSION: Histologically normal gallbladders with gallstones exhibited features of inflammation on immunohistochemistry.
Assuntos
Cálculos Biliares , Imuno-Histoquímica , Humanos , Cálculos Biliares/patologia , Cálculos Biliares/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/análise , Colecistite/patologia , Colecistite/metabolismo , Substância P/metabolismo , Vesícula Biliar/patologia , Vesícula Biliar/metabolismo , Receptores de Interleucina-2/metabolismo , Idoso , Doença Crônica , Biomarcadores/metabolismo , Biomarcadores/análise , Colecistite Aguda/patologia , Colecistite Aguda/metabolismo , Colecistite Aguda/cirurgiaRESUMO
Prostaglandin E2 (PGE2) is well known to promote tumor progression by boosting cancer cell proliferation while inhibiting anticancer immunity. Recent data from Lacher et al. and Morotti et al. demonstrate that one of the mechanisms through which PGE2 suppresses tumor-targeting immune responses involves downregulation of interleukin 2 (IL2) receptors and consequent inhibition of mitochondrial metabolism in T cells.
Assuntos
Ciclo-Oxigenase 2 , Dinoprostona , Mitocôndrias , Neoplasias , Humanos , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/tratamento farmacológico , Dinoprostona/metabolismo , Dinoprostona/imunologia , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/imunologia , Animais , Mitocôndrias/metabolismo , Mitocôndrias/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Receptores de Interleucina-2/metabolismo , Receptores de Interleucina-2/genética , Receptores de Interleucina-2/imunologiaRESUMO
A 61-year-old man with right hearing loss and staggering for seven months was diagnosed with sudden deafness although previous evaluation with MRI indicated minor abnormal findings. During follow-up, he developed hypogeusia, right facial nerve palsy, pain in right mandible, right-sided temporal pain, and cerebellar ataxia. Cerebrospinal fluid examination at admission revealed reduced glucose concentration and elevated soluble interleukin-2 receptor (sIL-2R) level, whereas serum sIL-2R level was within the normal range. Brain MRI showed a swollen contrast-enhanced lesion extending from the right internal auditory canal to the middle cerebellar peduncle. Gallium-67 (67Ga) single-photon emission-computed tomography-computed tomography (SPECT-CT) revealed abnormal accumulation at the lesion site. Pathologic analysis of the tumor after resection led to the diagnosis of primary central nervous system lymphoma. In the present case, the MRI and 67Ga SPECT-CT characteristics were distinct from those of vestibular schwannoma. In addition, elevation of sIL-2R in the cerebrospinal fluid but not in serum was useful for differential diagnosis.
Assuntos
Imageamento por Ressonância Magnética , Receptores de Interleucina-2 , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-2/sangue , Diagnóstico Diferencial , Orelha Interna/diagnóstico por imagem , Orelha Interna/patologia , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Perda Auditiva Súbita/etiologia , Perda Auditiva Súbita/diagnóstico , Radioisótopos de Gálio , Linfoma/diagnóstico , Neuroma Acústico/diagnóstico , Neuroma Acústico/diagnóstico por imagemRESUMO
OBJECTIVE: Tumor hypoxia induces the production of Hypoxia-Inducible Factor (HIF)-1 alpha, which interacts with NF-kB, leading to cancer proliferation and metastasis. This study investigated the effect of tumor hypoxia modulation using carbogen (95% O2 and 5% CO2) and nicotinamide on reducing soluble interleukin-2 receptor (sIL-2R) levels in newly diagnosed DLBCL patients with tissue overexpression of HIF-1α ≥10%. MATERIAL AND METHODS: A prospective randomized controlled clinical trial was conducted at Dr. Kariadi Hospital in Semarang, Indonesia, from 2021 to 2022. Newly diagnosed DLBCL patients with tissue HIF-1α ≥10% were randomized into an intervention group (nicotinamide 2,000 mg + carbogen 10 liters/min during R-CHOP) and a control group (R-CHOP alone) for one cycle. sIL-2R levels were measured in the blood before and after intervention. RESULTS: The intervention group showed a significant reduction in sIL-2R levels after chemotherapy (p=0.026), with 85% of samples exhibiting a decrease. In contrast, only 45% of samples in the control group demonstrated a decrease in sIL-2R levels (p=0.184). The median sIL-2R level decreased from 139.50 pg/mL to 70.50 pg/mL in the intervention group, while the control group exhibited an increase from 182.50 pg/mL to 250.00 pg/mL following one cycle of chemotherapy. CONCLUSION: Tumor hypoxia modulation led to a significant decrease in serum sIL-2R levels, potentially through improvements in the crosstalk between hypoxia and inflammation pathways.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Linfoma Difuso de Grandes Células B , Receptores de Interleucina-2 , Hipóxia Tumoral , Vincristina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Hipóxia Tumoral/efeitos dos fármacos , Estudos Prospectivos , Receptores de Interleucina-2/sangue , Receptores de Interleucina-2/metabolismo , Vincristina/uso terapêutico , Doxorrubicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Adulto , Prednisona/uso terapêutico , Prognóstico , Rituximab/uso terapêutico , Seguimentos , Idoso , Indonésia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/sangueRESUMO
Vigorous ex vivo expansion of NK-92 cells is a pivotal step for clinical adoptive immunotherapy. Interleukin-2 (IL-2) is identified as a key cytokine for NK-92 cells, and it can stimulate cell proliferation after binding to the IL-2 receptor (IL-2R). In this work, the differences in IL-2 consumption and IL-2R expression were investigated between the two culture modes. The results showed that suspension culture favored ex vivo expansion of NK-92 cells compared with static culture. The specific consumption rate of IL-2 in suspension culture was significantly higher than that in static culture. It was further found that the mRNA levels of the two IL-2R subunits remained unchanged in suspension culture, but the proportion of NK-92 cells expressing IL-2Rß was increased, and the fluorescence intensity of IL-2Rß was remarkably enhanced. Meanwhile, the proportion of cells expressing IL-2R receptor complex also increased significantly. Correspondingly, the phosphorylation of STAT5, a pivotal protein in the downstream signaling pathway of IL-2, was up-regulated. Notably, the expression level and colocalization coefficient of related endosomes during IL-2/IL-2R complex endocytosis were markedly elevated, suggesting the enhancement of IL-2 endocytosis. Taken together, these results implied that more IL-2 was needed to support cell growth in suspension culture. Therefore, the culture process was optimized from the perspective of cytokine utilization to further improve the NK-92 cell's expansion ability and function. This study provides valuable insight into the efficient ex vivo expansion of NK-92 cells.
Assuntos
Interleucina-2 , Células Matadoras Naturais , Interleucina-2/metabolismo , Células Matadoras Naturais/metabolismo , Receptores de Interleucina-2/metabolismo , Citocinas/metabolismo , Membrana CelularRESUMO
Interleukin-2 (IL-2) is a critical cytokine for T cell peripheral tolerance and immunity. Here, we review how IL-2 interaction with the high-affinity IL-2 receptor (IL-2R) supports the development and homeostasis of regulatory T cells and contributes to the differentiation of helper, cytotoxic, and memory T cells. A critical element for each T cell population is the expression of CD25 (Il2rα), which heightens the receptor affinity for IL-2. Signaling through the high-affinity IL-2R also reinvigorates CD8+ exhausted T (Tex) cells in response to checkpoint blockade. We consider the molecular underpinnings reflecting how IL-2R signaling impacts these various T cell subsets and the implications for enhancing IL-2-dependent immunotherapy of autoimmunity, other inflammatory disorders, and cancer.
Assuntos
Interleucina-2 , Neoplasias , Humanos , Interleucina-2/metabolismo , Autoimunidade , Receptores de Interleucina-2 , Subpopulações de Linfócitos TRESUMO
Aggressive types of adult T-cell leukemia-lymphoma (ATL), namely, the acute type, lymphoma type, and chronic type with poor prognostic factors, have a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (HSCT) may improve prognosis, relapse is common. In June 2021, tucidinostat was approved for relapsed or refractory ATL in Japan. We report a case of a 62-year-old man with relapsed ATL after allogeneic HSCT. In March 2017, he was diagnosed with ATL (acute type) and received two courses of mLSG-15 therapy. ATL cells reappeared in his peripheral blood, so he underwent allogeneic bone marrow transplantation in September 2017. In June 2021, his soluble interleukin-2 receptor (sIL-2R) level increased, and he began experiencing sensory abnormalities in his face and legs. In September, he developed respiratory failure and was diagnosed with relapse of ATL. He was again treated with mLSG-15. His sIL-2R normalized and the sensory abnormalities decreased, but sIL-2R rose again in February 2022. After tucidinostat treatment was initiated, sIL-2R normalized and the patient's general condition improved. Tucidinostat shows promise as an effective treatment for ATL that has relapsed after allogeneic HSCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva , Receptores de Interleucina-2RESUMO
OBJECTIVES: To evaluate the genetic polymorphisms in IL-2 and IL-2RA genes in schizophrenia (SCZ) patients by comparing them with healthy controls. METHODS: A sample of 127 patients with SCZ and 100 healthy volunteers were included in the case-control study. These individuals were consecutively selected from the Malazgirt State Hospital Psychiatry Outpatient Clinic in Mus, Turkey, over the three months from October 2020 to December 2020. The Structured Clinical Interview for DSM-5 Disorders, Clinician Version (SCID-5-CV) was used to confirm the diagnosis according to the DSM-5 criteria. In addition, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine gene polymorphisms from DNA material. RESULTS: Our findings indicated significant differences in the IL-2 genotype and allele frequencies between SCZ patients and the healthy control group. Specifically, the frequency of the homozygous GG genotype was notably higher in SCZ patients compared to the control group. Conversely, when comparing the IL-2RA genotype and allele frequencies of SCZ patients with the control group, no statistically significant differences were observed between the 2 groups. When compared to individuals with other genotypes, interaction analysis indicated that carriers of the GG/AG (IL-2/IL-2RA) genotype demonstrated a significantly increased risk of SCZ. CONCLUSION: In light of the analyses, our study indicates that while the IL-2 genotype polymorphism may be considered a risk factor for developing SCZ, the IL-2RA variant was not associated with SCZ among Turkish patients.
Assuntos
Interleucina-2 , Esquizofrenia , Animais , Humanos , Camundongos , Estudos de Casos e Controles , Epistasia Genética , Interleucina-2/genética , Polimorfismo Genético , Esquizofrenia/genética , Turquia , Receptores de Interleucina-2/metabolismoRESUMO
Marcadores sorológicos são rotineiramente utilizados na prática clínica para o estadiamento de linfomas e para a determinação de seu prognóstico em humanos. No entanto, pouco se sabe sobre sua utilização em cães, mesmo os linfomas sendo neoplasias com alta prevalência nessa espécie. No presente estudo, as concentrações séricas do receptor solúvel de interleucina-2 (sIL-2R) e do antígeno do câncer 125 (CA 125) foram mensurados em 10 cães saudáveis e em 15 cães com linfoma cutâneo, utilizando-se o kit ELISA canino e a leitura em um Stat Fax modelo 2100 (sIL-2R), bem como o kit ELISA humano e a leitura pelo ELISYS UNO humano (CA 125). Os resultados mostraram que não houve diferença significativa (P<0,05) nas concentrações dos marcadores entre os grupos. Além disso, os resultados não apontaram significância clínica no estadiamento tumoral e estabelecimento do prognóstico em cães diagnosticados com linfoma cutâneo.(AU)
Assuntos
Animais , Cães , Biomarcadores/sangue , Receptores de Interleucina-2/sangue , Antígeno Ca-125/sangue , Linfoma/veterinária , Prognóstico , Neoplasias Cutâneas/veterináriaRESUMO
El síndrome de activación macrofágica (SAM) presenta criterios clínicos y de laboratorio establecidos. Presentamos el caso de un adolescente varón con debut de Lupus eritematoso generalizado pediátrico grave, donde su manifestación principal fue un SAM y el receptor de interleucina 2 soluble en suero (IL-2rs) o CD25 soluble (CD25s) aumentado resultó clave en la confirmación diagnóstica, en el tratamiento y pronóstico de su enfermedad. Sin embargo, este receptor de citocinas no se mide habitualmente en la práctica clínica.
Macrophage activation syndrome (MAS) presents established clinical and laboratory criteria. We present the case of a male adolescent with the onset of severe pediatric systemic Lupus erythematosus, manifested mainly by MAS and how a laboratory marker, serum soluble interleukin-2 receptor (IL-2rs) or altered soluble CD25(CD25s), played a key role in treatment and prognosis of the disease. However, this cytokine receptor is rarely measured in clinical practice.
Assuntos
Humanos , Masculino , Criança , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/terapia , Tórax/diagnóstico por imagem , Radiografia Torácica/métodos , Receptores de Interleucina-2 , Síndrome de Ativação Macrofágica/patologia , Lúpus Eritematoso SistêmicoRESUMO
Se realizó un estudio aleatorio para determinar los niveles de interleucina-2 (IL-2) y su receptor soluble (RsIL-2) en pacientes operados y transfundidos, antes de la cirugía, en el hemoderivado y 24 h después de la transfusión y para relacionar los niveles de IL-2 y RsIL-2 con cada período. Mediante inmunoensayo enzimático se determinaron los niveles de de IL-2 y RsIL-2 en 40 pacientes operados, antes de la cirugía, en los derivados sanguíneos y 24 horas después de la transfusión. Se obtuvieron valores promedio de 3,98 U/mL; 3,18 U/mL e indetectable para IL-2 y de de 678,2; 1 402 y 90,34 pg/mL para RsIL-2, en los períodos respectivos. El declive de la función linfocitaria después de cirugía y transfusión se atribuye a cambios intrínsecos o a la redistribución de células T reactivas de la sangre hacia los tejidos, a factores séricos como prostaglandinas y corticoesteroides, inhibidores de IL-2 que, con los elevados valores de RsIL-2 hallados en la bolsa, explican los niveles indetectables de IL-2 a las 24 horas de la transfusión(AU)
He/she was carried out an aleatory study to determine the interleucina-2 levels (IL-2) and their soluble receiver (RsIL-2) in operated patients and transfused, before the surgery, in the hemoderivado and 24 h after the transfusion and to relate the levels of IL-2 and RsIL-2 with every period. By means of enzymatic inmunoensayo the levels were determined of of IL-2 and RsIL-2 in 40 operated patients, before the surgery, in those derived sanguine and 24 hours after the transfusion. Values average of 3,98 U/mL were obtained; 3,18 U/mL and indetectable for IL-2 and of of 678,2; 1 402 and 90,34 pg/mL for RsIL-2, in the respective periods. The decline of the function linfocitaria after surgery and transfusion is attributed to intrinsic changes or the redistribution of cells T you reactivate of the blood toward the fabrics, to factors séricos like prostaglandinas and corticoesteroides, inhibitors of IL-2 that, with the high values of RsIL-2 found in the bag, they explain the levels indetectables of IL-2 at the 24 hours of the transfusion(AU)
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Operatórios/métodos , Transfusão de Sangue/métodos , Receptores de Interleucina-2/administração & dosagem , Interleucina-2/sangueRESUMO
The phenotypic features acquired subsequent to antigen-specific stimulation in vitro were evaluated by means of the kinetic expressions of CD69 and CD25 activation molecules on T lymphocytes and assayed by flow cytometry in response to PPD, Ag85B, and ferritin in PPD-positive healthy control individuals. In response to PHA, CD69 staining on both CD4+ and CD8+ T cells became initially marked after 4 h, peaked at 24 h, and quickly decreased after 120 h. For CD25, a latter expression was detected around 8 h, having increased after 96 h. As expected, the response rate to the mycobacterial antigens was much lower than that to the mitogen. Positive staining was high after 96 h for CD25 and after 24 h for CD69. CD69 expression was significantly enhanced (p < 0.05) on CD8+ as compared to CD4+ T cells. High levels were also found between 96-120 h. Regarding Ag85B, CD25+ cells were mostly CD4+ instead of CD8+ T cells. Moreover, in response to ferritin, a lower CD25 expression was noted. The present data will allow further characterization of the immune response to new mycobacterial-specific antigens and their evaluation for possible inclusion in developing new diagnostic techniques for tuberculosis as well in a new vaccine to prevent the disease
Assuntos
Antígenos de Bactérias , Antígenos CD , Antígenos de Diferenciação de Linfócitos T , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Ativação Linfocitária/imunologia , Mycobacterium tuberculosis , Receptores de Interleucina-2 , Aciltransferases , Proteínas de Bactérias , Ferritinas , Citometria de Fluxo , TuberculinaRESUMO
La espirulina es un alga cianofícea que es utilizada como aditivo alimentario y por sus propiedades medicinales. Se realizó este trabajo para evaluar el efecto in vitro de la espirulina (Spirel, Génix, Ciudad de La Habana, Cuba) en 14 donantes sanos del Instituto de Hematología e Inmunología mediante las pruebas de transformación linfoblástica con criterio de timidina tritiada; en la expresión de los antígenos de activación HLA-DR y CD-25 por el ultramicrométodo inmunocitoquímico (UMICIQ) y la formación de roseta activa. En la transformación blástica no se hallaron diferencias estadísticamente significativas entre las condiciones experimentales con y sin espirulina, mientras que se hallaron diferencias estadísticamente significativas al aplicar la t de Student para muestras pareadas entre las condiciones experimentales con y sin espirulina, tanto en la expresión de los antígenos de activación como en la formación de roseta activa. Se concluye que la espirulina de producción nacional influye in vitro en el proceso de activación de los linfocitos humanos.
Assuntos
Humanos , Cianobactérias , Aditivos Alimentares , Antígenos HLA-DR , Técnicas In Vitro , Receptores de Interleucina-2 , Formação de RosetaRESUMO
An association between depression and altered immune and hormonal systems has been suggested by the results of many studies. In the present study we carried out immune and hormonal measurements in 40 non-medicated, ambulatory adult patients with depression determined by CID-10 criteria and compared with 34 healthy nondepressed subjects. The severity of the condition was determined with the Hamilton Depression Rating Scale. Of 40 depressed patients, 31 had very severe and 9 severe or moderate depression, 29 (72.5 percent) were females and 11 (27.5 percent) were males (2.6:1 ratio). The results revealed a significant reduction of albumin and elevation of alpha-1, alpha-2 and beta-globulins, and soluble IL-2 receptor in patients with depression compared to the values obtained for nondepressed subjects (P<0.05). The decrease lymphocyte proliferation in response to a mitogen was significantly lower in severely or moderately depressed patients when compared to control (P<0.05). These data confirm the immunological disturbance of acute phase proteins and cellular immune response in patients with depression. Other results may be explained by a variety of interacting factors such as number of patients, age, sex, and the nature, severity and/or duration of depression. Thus, the data obtained should be interpreted with caution and the precise clinical relevance of these findings requires further investigation
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Proteínas Sanguíneas , Citocinas , Depressão , Hormônios , Divisão Celular , Citocinas , Hormônios , Linfócitos , Pacientes Ambulatoriais , Receptores de Interleucina-2 , Albumina Sérica , Soroglobulinas , Índice de Gravidade de DoençaRESUMO
This paper reports the overall effects of three lectins, extracted from Canavalia brasiliensis, Dioclea violacea, and D. grandiflora, on BALB/c mice popliteal draining lymph nodes. These lectins have presented high stimulatory capacity on lymph node T cells. Additionally, they were able to induce apoptosis and inflammation (frequently associated with high endothelial venule necrosis). The data presented here suggest that the Diocleinae lectins studied can stimulate in vivo T cell activation and apoptosis, as well as present important side effects