RESUMO
Sarcoidosis is a multisystem granulomatous disease of unknown origin. Ninety percent of patients with sarcoidosis have lung involvement. The onset can be acute or non-acute and the severity of sarcoidosis ranges widely from asymptomatic patients with accidental radiographic findings to patients with severe organ involvement. This case control analytic prospective study was conducted at the Chest Clinic, Al Zahraa hospital, to assess the diagnostic value of serum soluble interleukin 2 receptor (sIL-2R), cluster of differentiation 4 (CD4)/CD8 ratio and CD103 in sarcoidosis. We investigated the value of serum sIL-2R using ELISA and blood CD103, blood CD4/CD8 ratio using flow cytometry for 30 cases of sarcoidosis in different stages and 30 control persons to detect their use as a marker for diagnosis. We found a significant increase in sIL-2R in the sarcoidosis group as compared to the control group (pË0.0001), while there was a significant decrease in CD103/CD4 in sarcoidosis group as compared to the control group (p < 0.001). In conclusion, sIL-2R and CD103 can be used as diagnostic markers for sarcoidosis.
Assuntos
Sarcoidose , Humanos , Estudos Prospectivos , Sarcoidose/diagnóstico , Biomarcadores , Estudos de Casos e Controles , Receptores de Interleucina-2/análiseRESUMO
BACKGROUND: Serum soluble interleukin-2 receptor (sIL-2R) is recognized as a marker of T-cell activation and is abnormally elevated in sarcoidosis. However, its value for stage I sarcoidosis in benign granulomatous diseases is unclear. METHODS: We enrolled 33 stage I sarcoidosis patients, 17 lymph node tuberculosis patients, 15 reactive lymphadenopathy patients, and 11 healthy controls. Serum biomarkers concentrations were collected and collated. RESULTS: Serum sIL-2R concentrations were the highest in stage I sarcoidosis. The AUC of serum sIL-2R for stage I sarcoidosis was 0.7452 in all subjects and 0.6861 in granulomatous diseases. The AUCs of two combined diagnostic forms, sIL-2R with angiotensin-converting enzyme (ACE) and sIL-2R with ACE, erythrocyte sedimentation rate (ESR), and lactate dehydrogenase (LDH) were 0.7994 and 0.891 in all subjects, respectively. In granulomatous disease groups for ROC analysis, the best cut-off value of sIL-2R was 745.00 U/ml with 48.50% sensitivity and 84.40% specificity. The combination of four parameters increased the diagnostic accuracy for stage I sarcoidosis in granulomatous diseases (74.10% sensitivity and 100% specificity). Serum sIL-2R concentrations were positively correlated with serum ACE (r = 0.4652, P = 0.0126). CONCLUSION: Serum sIL-2R appeared to be valuable in identifying stage I sarcoidosis in a group of benign granulomatous disorders.
Assuntos
Linfadenopatia , Sarcoidose , Humanos , Receptores de Interleucina-2/análise , Sarcoidose/diagnóstico , Biomarcadores , Curva ROCRESUMO
Objective: To explore the clinical utility of tumor-specific growth factor (TSGF) and the soluble interleukin-2 (IL-2) receptor (sIL-2R) as immune-related factors for predicting lymph node metastases (LNM) of papillary thyroid carcinoma (PTC). Methods: A total of 206 patients with PTC subjected to curative surgery were enrolled. All patients had complete medical records. Serum levels of TSGF were detected using Automatic Biochemistry Analyzer and the serum sIL-2R concentration was detected by enzyme-linked immunosorbent assay (ELISA). Furthermore, we analyzed the relationship between the two indicators and the clinicopathological characteristics and assessed their effect on lymphatic metastasis in patients with PTC by logistic regression analysis. Results: Receiver operating characteristic (ROC) analysis revealed that the determined cut-off value of serum TSGF and sIL-2R was 63.35 U/mL and 507 U/mL, respectively. Serum TSGF was associated with focality (χ 2 = 4.97, P = 0.026) and lymphatic metastasis (χ 2 = 4.154, P = 0.042), while serum sIL-2R was remarkably related to gender (χ 2 = 4.464, P = 0.035). Univariate logistic regression analysis indicated that age, tumor size, serum TSGF level, capsule invasion, and nodular goiter were the lymphatic metastasis-related factor of PTC. Multivariate regression analysis revealed that age > 45 years was a protective factor (OR: 0.4, 95% CI: 0.206-0.777, P = 0.007). Conversely, larger tumor size (OR: 4.594, 95% CI: 2.127-9.921, P = 0.000), higher serum TSGF levels (OR: 1.888, 95% CI: 1.009-3.533, P = 0.047), and capsule invasion (OR: 1.939, 95% CI: 1.009-3.726, P = 0.047) were associated with an increased risk of LNM. Conclusion: Serum TSGF levels were identified as an independent factor for LNM in patients with PTC.
Assuntos
Receptores de Interleucina-2 , Neoplasias da Glândula Tireoide , Antígenos de Neoplasias , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Metástase Linfática , Pessoa de Meia-Idade , Proteínas de Neoplasias , Receptores de Interleucina-2/análise , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologiaRESUMO
Objective: The aim of this study is to explore the clinical application value of high-frequency ultrasound combined with detection of serum high mobility group box (HMGB-1), soluble IL-2 receptor (SIL-2R), and thyroglobulin antibody (TgAb) in diagnosing thyroid cancer. Methods: By means of retrospective study, 50 thyroid cancer patients treated in our hospital from January 2019 to January 2021 were selected as the thyroid cancer group, 50 patients with benign thyroid lesions were included in the benign lesion group, and 50 healthy individuals examined in our hospital in the same period were included in the control group. All study objects received high-frequency ultrasound examination, and at the same time, their serum HMGB-1, SIL-2R, and TgAb levels were measured. After that, the results of high-frequency ultrasound examination were analyzed, the diagnostic efficacy of different diagnosis methods was explored, and receiver operating characteristic (ROC) curves were plotted. Results: According to the results of high-frequency ultrasound examination, there were significant differences in echogenicity surrounding and inside the lesion, calcification, blood flow distribution, and blood flow parameters between the thyroid cancer group and the benign lesion group (P < 0.001); the HMGB-1, SIL-2R, and TgAb levels were statistically different among the three groups (P < 0.001), and the level values of HMGB-1, SIL-2R, and TgAb of the thyroid cancer group were, respectively, (12.26 ± 1.32) ng/ml, (108.65 ± 9.75) pmol/L, and (690.65 ± 34.47) IU/mL; the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of high-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb were, respectively, 98.0%, 95.0%, 90.7%, and 99.0%, and AUC (95%CI) = 0.965 (0.931-0.999). Conclusion: High-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb has a good value in diagnosing thyroid cancer, which should be promoted in practice.
Assuntos
Autoanticorpos , Proteína HMGB1 , Receptores de Interleucina-2 , Neoplasias da Glândula Tireoide , Autoanticorpos/análise , Proteína HMGB1/análise , Humanos , Receptores de Interleucina-2/análise , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , UltrassonografiaRESUMO
PURPOSE: Epithelial ovarian cancer (EOC) is regarded as the deadliest gynecological cancer, and the demand for novel noninvasive prognostic biomarkers remains significant. This study aimed to investigate the prognostic value of preoperative blood biomarkers in EOC patients. METHODS: In total, 73 patients who had undergone ovarian mass resection were enrolled. Serum concentration of biomarkers, including soluble interleukin 2 receptor α (sIL-2R), was measured 1-2 weeks before surgery. Independent prognostic factors for progression-free survival (PFS) were investigated with multivariate Cox regression analysis. A prognostic model was subsequently developed and evaluated by discrimination, calibration and clinical net benefit. Furthermore, transcriptome data of 376 EOC cases from The Cancer Genome Atlas (TCGA) were analyzed with ESTIMATE, CIBERSORT and Maftools algorithm to evaluate the correlation of IL2RA expression with tumor immune microenvironment and immunotherapeutic response. RESULTS: High sIL-2R concentration was found to be the only significant prognostic blood biomarker for PFS by multivariate Cox regression analysis in our center. A prognostic nomogram was developed with satisfactory discrimination, calibration and clinical net benefit. In addition, higher IL2RA expression was significantly associated with higher immune scores, activated CD4+ T cells, M2 macrophages and resting dendritic cells in TCGA data. Furthermore, IL2RA expression was closely related to TMB scores. CONCLUSIONS: sIL-2R is a potential prognostic immune biomarker for EOC patients, and a comprehensive prognostic model comprising sIL-2R with satisfactory discrimination and clinical appliance was developed. Therefore, we recommend routine sIL-2R testing in EOC patients.
Assuntos
Neoplasias Ovarianas , Biomarcadores , Carcinoma Epitelial do Ovário/genética , Feminino , Humanos , Subunidade alfa de Receptor de Interleucina-2 , Prognóstico , Receptores de Interleucina-2/análise , Receptores de Interleucina-2/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Our previous study demonstrated that the soluble interleukin-2 receptor (sIL-2R) index, defined as the ratio of serum sIL-2R levels at neutrophil engraftment to that before conditioning, is a biomarker that can predict acute graft-vs-host disease (GVHD) after unrelated bone marrow transplantation. In the present study, we evaluated the significance of the sIL-2R index among patients who underwent cord blood transplantation (CBT). METHODS: We retrospectively analyzed 31 patients who underwent single-unit CBT as their first transplantation for hematologic malignancies. RESULTS: The median sIL-2R index was 4.2. The cumulative incidence of grade II to IV acute GVHD was not associated with the sIL-2R index. However, the cumulative incidence of relapse at 3 years after transplantation was significantly lower, with an sIL-2R index ≥ 3.7 than with an index < 3.7 (12.8% vs 50.0%; P = .04). As a result, the probability of overall survival at 3 years after transplantation was significantly higher in the former group than in the latter (79.8% vs 20.0%; P < .01). Only the dose of corticosteroid administered in the pre-engraftment period influenced the sIL-2 index. CONCLUSION: The sIL-2R index can predict the incidence of relapse and probability of survival after CBT, possibly reflecting a graft-vs-leukemia effect.
Assuntos
Biomarcadores/sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/sangue , Recidiva Local de Neoplasia/sangue , Receptores de Interleucina-2/metabolismo , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/cirurgia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Receptores de Interleucina-2/análise , Estudos RetrospectivosRESUMO
Tumor biopsy is essential for the definitive diagnosis of central nervous system (CNS) lymphoma. However, the biopsy procedure carries the risk of complications such as bleeding, convulsions, and infection. Cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG), soluble IL-2 receptor (sIL-2R), and interleukin-10 (IL-10) are known to be useful diagnostic biomarkers for CNS lymphoma. The C-X-C motif chemokine ligand 13 (CXCL13) was recently reported to be another useful biomarker for CNS lymphoma. The purpose of this study is to establish a diagnostic algorithm that can avoid biopsy by combining these diagnostic biomarkers. In the first, we conducted a case-control study (n = 248) demonstrating that the CSF CXCL13 concentration was significantly increased in CNS lymphoma patients compared with various other brain diseases (AUC = 0.981). We established a multi-marker diagnostic model using CSF CXCL13, IL-10, ß2-MG, and sIL-2R from the results of the case-control study and then applied the model to a prospective study (n = 104) to evaluate its utility. The multi-marker diagnostic algorithms had excellent diagnostic performance: the sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 97%, 94%, and 99%, respectively. In addition, CSF CXCL13 was a prognostic biomarker for CNS lymphoma patients. Our study suggests that multi-marker algorithms are important diagnostic tools for patients with CNS lymphoma.
Assuntos
Algoritmos , Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Quimiocina CXCL13/líquido cefalorraquidiano , Interleucina-10/líquido cefalorraquidiano , Linfoma não Hodgkin/diagnóstico , Receptores de Interleucina-2/análise , Microglobulina beta-2/líquido cefalorraquidiano , Estudos de Casos e Controles , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Seguimentos , Humanos , Linfoma não Hodgkin/líquido cefalorraquidiano , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: It is often difficult to diagnose central nervous system (CNS) inflammatory demyelinating diseases (IDDs) because they are similar to CNS lymphoma and glioma. OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) analysis can differentiate CNS IDDs from CNS lymphoma and glioma. METHODS: We measured CSF cell counts; concentrations of proteins, glucose, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), and myelin basic protein; and IgG index in patients with multiple sclerosis (MS, n = 64), neuromyelitis optica spectrum disorder (NMOSD, n = 35), tumefactive demyelinating lesion (TDL, n = 17), CNS lymphoma ( n = 12), or glioma ( n = 10). We detected diagnostic markers using logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: Median CSF IL-10 and sIL-2R levels were higher in CNS lymphoma patients than in MS, NMOSD, or TDL patients. Logistic regression revealed that CSF sIL-2R levels predicted CNS lymphoma. In the ROC analysis of CSF sIL-2R levels, the area under the curve was 0.867, and the sensitivity and specificity were 83.3% and 90.0%, respectively. CONCLUSION: CSF sIL-2R levels can be used to differentiate CNS lymphoma from CNS IDDs. Further studies may identify other applications of CSF as a diagnostic biomarker.
Assuntos
Biomarcadores/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/líquido cefalorraquidiano , Linfoma/líquido cefalorraquidiano , Receptores de Interleucina-2/análise , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/diagnóstico , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Linfoma/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
A smouldering adult T-cell leukaemia/lymphoma (ATLL) patient was admitted because of multiple erosions in the colon, which were infiltrated by a mixed population of lymphocytes. PET/CT demonstrated diffuse 18F-Fluorodeoxyglucose accumulation in the whole colon accompanied by multiple lymph node swelling. Histological examinations of lymph node suggested aggressive transformation to lymphoma type of ATLL. However, the general condition worsened with extremely elevated LDH, cytomegalovirus pp65 and sIL-2R after the administration of prednisolone. By contrast, subsequent administration of ganciclovir with tapered prednisolone ameliorated the laboratory findings. Differential diagnosis for aggressive ATLL and serious cytomegalovirus infection is needed.
Assuntos
Colite/diagnóstico , Infecções por Citomegalovirus/diagnóstico , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Receptores de Interleucina-2/análise , Idoso , Colite/imunologia , Colite/patologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , Diagnóstico Diferencial , Fluordesoxiglucose F18 , Humanos , Leucemia-Linfoma de Células T do Adulto/patologia , Linfonodos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
Schizophrenia, bipolar disorder and major depressive disorder (MDD) have all been associated with aberrant blood cytokine levels; however, neither the pattern of cytokine alterations nor the impact of clinical status have been compared across disorders. We performed a meta-analysis of blood cytokines in acutely and chronically ill patients with these major psychiatric disorders. Articles were identified by searching the PubMed, PsycInfo and Web of Science, and the reference lists of these studies. Sixty-eight studies met the inclusion criteria (40 schizophrenia, 10 bipolar disorder and 18 MDD) for acutely ill patients. Forty-six studies met the inclusion criteria (18 schizophrenia, 16 bipolar disorder and 12 MDD) for chronically ill patients. Levels of two cytokines (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)), one soluble cytokine receptor (sIL-2R), and one cytokine receptor antagonist (IL-1RA) were significantly increased in acutely ill patients with schizophrenia, bipolar mania and MDD compared with controls (P<0.01). Following treatment of the acute illness, IL-6 levels significantly decreased in both schizophrenia and MDD (P<0.01); sIL-2R levels increased in schizophrenia; and IL-1RA levels in bipolar mania decreased. In chronically ill patients, the levels of IL-6 were significantly increased in schizophrenia, euthymic (but not depressed) bipolar disorder and MDD compared with controls (P<0.01). The levels of IL-1ß and sIL-2R were significantly increased in both chronic schizophrenia and euthymic bipolar disorder. Overall, there were similarities in the pattern of cytokine alterations in schizophrenia, bipolar disorder and MDD during acute and chronic phases of illness, raising the possibility of common underlying pathways for immune dysfunction. Effects of treatment on cytokines were more robust for schizophrenia and MDD, but were more frequently studied than for acute mania. These findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders.
Assuntos
Transtorno Bipolar/metabolismo , Depressão/metabolismo , Esquizofrenia/metabolismo , Adulto , Transtorno Bipolar/sangue , Citocinas/análise , Citocinas/sangue , Depressão/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/análise , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-6/análise , Interleucina-6/sangue , Masculino , Transtornos Psicóticos/sangue , Transtornos Psicóticos/metabolismo , Receptores de Interleucina-2/análise , Receptores de Interleucina-2/sangue , Esquizofrenia/sangue , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVES: The magnitude and role of the cellular immune response following pediatric traumatic brain injury remains unknown. We tested the hypothesis that macrophage/microglia and T-cell activation occurs following pediatric traumatic brain injury by measuring cerebrospinal fluid levels of soluble cluster of differentiation 163 and ferritin and soluble interleukin-2 receptor α, respectively, and determined whether these biomarkers were associated with relevant clinical variables and outcome. DESIGN: Retrospective analysis of samples from an established, single-center cerebrospinal fluid bank. SETTING: PICU in a tertiary children's hospital. PATIENTS: Sixty-six pediatric patients after severe traumatic brain injury (Glasgow Coma Scale score < 8) who were 1 month to 16 years old and 17 control patients who were 1 month to 14 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor α were determined by enzyme-linked immunosorbent assay at two time points (t1 = 17 ± 10 hr; t2 = 72 ± 15 hr) for each traumatic brain injury patient. Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor α after traumatic brain injury were compared with controls and analyzed for associations with age, patient sex, initial Glasgow Coma Scale score, diagnosis of abusive head trauma, the presence of hemorrhage on CT scan, and Glasgow Outcome Scale score. Cerebrospinal fluid level of soluble cluster of differentiation 163 was increased in traumatic brain injury patients at t2 versus t1 and controls (median, 95.4 ng/mL [interquartile range, 21.8-134.0 ng/mL] vs 31.0 ng/mL [5.7-77.7 ng/mL] and 27.8 ng/mL [19.1-43.1 ng/mL], respectively; p < 0.05). Cerebrospinal fluid level of ferritin was increased in traumatic brain injury patients at t2 and t1 versus controls (8.3 ng/mL [<7.5-19.8 ng/mL] and 8.9 ng/mL [<7.5-26.7 ng/mL] vs <7.5 ng/mL below lower limit of detection, respectively; p < 0.05). Cerebrospinal fluid levels of soluble interleukin-2 receptor α in traumatic brain injury patients at t2 and t1 were not different versus controls. Multivariate regression revealed associations between high ferritin and age 4 years or younger, lower Glasgow Coma Scale score, abusive head trauma, and unfavorable Glasgow Outcome Scale score. CONCLUSIONS: Children with traumatic brain injury demonstrate evidence for macrophage activation after traumatic brain injury, and in terms of cerebrospinal fluid ferritin, this appears more prominent with young age, initial injury severity, abusive head trauma, and unfavorable outcome. Further study is needed to determine whether biomarkers of macrophage activation may be used to discriminate between aberrant and adaptive immune responses and whether inflammation represents a therapeutic target after traumatic brain injury.
Assuntos
Antígenos CD/líquido cefalorraquidiano , Antígenos de Diferenciação Mielomonocítica/líquido cefalorraquidiano , Lesões Encefálicas/líquido cefalorraquidiano , Lesões Encefálicas/imunologia , Ferritinas/líquido cefalorraquidiano , Receptores de Interleucina-2/análise , Adolescente , Fatores Etários , Biomarcadores/líquido cefalorraquidiano , Lesões Encefálicas/etiologia , Estudos de Casos e Controles , Criança , Maus-Tratos Infantis/diagnóstico , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Recém-Nascido , Ativação Linfocitária , Ativação de Macrófagos , Macrófagos/imunologia , Masculino , Microglia/imunologia , Receptores de Superfície Celular , Estudos Retrospectivos , Linfócitos T/imunologiaRESUMO
The interleukin-9 receptor (IL-9R) consists of an α subunit and a γ(c) chain that are shared with other cytokine receptors, including interleukin-2 receptor (IL-2R), an important regulator of T cells. We previously showed that IL-2R is expressed in common clusters with major histocompatibility complex (MHC) glycoproteins in lipid rafts of human T lymphoma cells, which raised the question about what the relationship between clusters of IL-2R/MHC and IL-9R is. Confocal microscopy colocalization and fluorescence resonance energy transfer experiments capable of detecting membrane protein organization at different size scales revealed nonrandom association of IL-9R with IL-2R/MHC clusters at the surface of human T lymphoma cells. Accommodation of IL-9Rα in membrane areas segregated from the IL-2R/MHC domains was also detected. The bipartite nature of IL-9R distribution was mirrored by signal transducer and activator of transcription (STAT) activation results. Our data indicate that co-compartmentalization with MHC glycoproteins is a general property of γ(c) receptors. Distribution of receptor chains between different membrane domains may regulate their function.
Assuntos
Glicoproteínas/análise , Antígenos HLA/análise , Linfoma de Células T/patologia , Receptores de Interleucina-2/análise , Receptores de Interleucina-9/análise , Linfócitos T/patologia , Linhagem Celular Tumoral , Transferência Ressonante de Energia de Fluorescência , Humanos , Complexo Principal de Histocompatibilidade , Microscopia Confocal , Linfócitos T/químicaRESUMO
BACKGROUND: More than two-thirds of depressed patients complain of somatic and pain symptoms, which are frequently regarded as a psychological reaction. Although there is a growing body of evidence showing that depression is related to immune abnormalities, few studies have investigated the association between inflammatory cytokines and somatic/pain symptoms. METHOD: Patients with depressive disorder but without any medical disorders, and age/gender/body mass index (BMI)-matched healthy subjects were enrolled. All the subjects completed the self-rating scales of the Beck Depression Inventory-II and the Depression and Somatic Symptoms Scale, which was comprised of depressive, somatic, and pain subscales. Pro-inflammatory cytokines, including C-reactive protein (CRP), interleukin-2 receptor (sIL-2R), soluble interleukin 6 receptor (sIL-6R), soluble TNF-receptors (sTNF-R), soluble P-selectin (sP-selectin), monocyte chemotactic protein-1 (MCP-1), and adiponectin, were assessed by enzyme-linked immunosorbent assays. RESULTS: In all, 109 patients with depressive disorder and 126 normal controls were enrolled. The patients with depressive disorder had significantly more severe depression, somatic and pain symptoms (all p<0.001), and higher levels of sIL-2R (p<0.0001), sTNF-R (p<0.001), and sP-selectin (p=0.005) than the normal control group. Using multivariate regression analysis with controlling of age, gender, BMI, and other pro-inflammatory cytokines, sIL-2R was the most significant predictor for depressive symptoms (p<0.0001); with further controlling of severity of depressive symptom, sP-selectin was the only predictor for somatic (p=0.002) and pain (p=0.059) symptoms. CONCLUSION: The elevated sP-selectin associated with somatic symptoms in depression, may indicate early micro-vascular changes occur subtly, and provide neurobiological evidence for somatic and pain symptom in depression.
Assuntos
Citocinas/efeitos adversos , Depressão/epidemiologia , Dor/epidemiologia , Transtornos Somatoformes/epidemiologia , Adiponectina/efeitos adversos , Adiponectina/análise , Adulto , Proteína C-Reativa/efeitos adversos , Proteína C-Reativa/análise , Estudos de Casos e Controles , Quimiocina CCL2/efeitos adversos , Quimiocina CCL2/análise , Citocinas/análise , Depressão/sangue , Depressão/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/efeitos adversos , Selectina-P/análise , Dor/sangue , Dor/imunologia , Escalas de Graduação Psiquiátrica , Receptores de Interleucina-2/análise , Receptores de Interleucina-6/análise , Receptores do Fator de Necrose Tumoral/análise , Índice de Gravidade de Doença , Transtornos Somatoformes/sangue , Transtornos Somatoformes/imunologiaRESUMO
Cutaneous mast cell tumours (MCTs) are among the most important skin tumours in dogs. Apart from c-KIT mutations, which are present in <18% of MCTs, little is known of the mechanisms of MCT development and independent growth of tumour cells. Recently, the α-subunit (CD25) of the interleukin (IL)-2 receptor (IL-2R) has been found to be expressed by canine cutaneous MCTs and this expression is negatively correlated with tumour grade. We thus hypothesized that the other two subunits of the IL-2R and the ligand IL-2 are also expressed and that IL-2-dependent pathways may have an impact on MCT development and independent tumour cell growth. Messenger RNA and protein expression levels of the IL-2R ß-subunit (CD122), the IL-2R γ-subunit (CD132) and IL-2 were analyzed in canine cutaneous MCTs and compared with tumour grade and c-KIT mutation status. Eighty-six percent of the tumours expressed both subunits of the IL-2R and 64% expressed IL-2. In addition, neoplastic mast cells seem able to bind IL-2. IL-2Rγ and IL-2 protein expression levels were significantly decreased in higher grade tumours and IL-2 expression was significantly decreased in c-KIT mutated tumours. Thus, expression of the complete IL-2R and its ligand by canine cutaneous MCTs indicates a potential impact of IL-2R signalling in MCT development and tumour cell proliferation. The decrease in IL-2R expression with increasing histological evidence of malignancy suggests that the IL-2R may be more relevant for early MCT development and well-differentiated tumours.
Assuntos
Doenças do Cão/metabolismo , Mastocitose Cutânea/veterinária , Receptores de Interleucina-2/biossíntese , Neoplasias Cutâneas/veterinária , Animais , Biomarcadores Tumorais/análise , Cães , Imuno-Histoquímica , Interleucina-2/metabolismo , Mastocitose Cutânea/genética , Mastocitose Cutânea/metabolismo , Gradação de Tumores , Subunidades Proteicas/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Interleucina-2/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismoRESUMO
The clinical significance of serum soluble interleukin-2 receptor (sIL2R) levels was retrospectively assessed in patients with advanced diffuse large B-cell lymphoma (DLBCL). Twenty-one patients, who were newly-diagnosed with advanced DLBCL (stage III and IV) between 2006 and 2009, were evaluated. The median follow-up period was 37 months. All patients received 6-8 cycles of chemotherapy with rituximab in combination with doxorubicin, cyclophosphamide, vincristine, and prednisolone (CHOP)-like regimens and attained complete remission. Although all patients reached complete remission, six patients experienced disease relapse within 1 year after treatment completion. The overall survival was significantly poorer in patients with relapse than in patients with durable remission. The sIL2R levels after the sixth cycle of treatment were significantly higher in the relapse group than in the non-relapse group. Thus, the present study suggests sIL2R levels to be a valuable predictor for the prognosis of patients with advanced DLBCL.
Assuntos
Biomarcadores Tumorais/sangue , Linfoma Difuso de Grandes Células B/sangue , Recidiva Local de Neoplasia/sangue , Receptores de Interleucina-2/sangue , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/análise , Ciclofosfamida , Doxorrubicina , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prednisona , Prognóstico , Receptores de Interleucina-2/análise , Estudos Retrospectivos , Rituximab , VincristinaRESUMO
BACKGROUND: Many studies have explored the association between soluble interleukin-2 receptor (sIL-2R), cytokines and major depressive disorder (MDD). However, the results of these studies were not consistent. The aim of our study is to compare the levels of sIL-2R and cytokines in the blood between MDD patients and controls by a meta-analysis and to identify moderators accounting for potential heterogeneity in the levels of sIL-2R and cytokines in MDD patients versus controls by meta-regression analyses. METHODS: A comprehensive literature search was performed to identify studies comparing the levels of sIL-2R and cytokines between MDD patients and controls. We pooled the effect sizes for standardized mean differences (SMD) of the levels of sIL-2R and cytokines. We also performed meta-regression and sensitivity analyses to investigate the roles of age, gender, sample type, ethnic origin and selected studies' quality in explaining potential heterogeneity and differences in results respectively. RESULTS: Twenty-nine studies were selected for this analysis. The levels of sIL-2R, TNF-α and IL-6 in MDD patients were significantly higher than those of healthy controls (SMD=0.555, p<0.001, SMD=0.567, p=0.010; SMD=0.680, p<0.001). Mean age of all subjects was a significant moderator to explain the high heterogeneity of IL-6. Sensitivity analysis found that European but not non-European subjects have higher levels difference of sIL-2R, TNF-α and IL-1ß between MDD patients and controls. LIMITATION: The severity of MDD was not considered. CONCLUSION: The blood levels of sIL-2R, TNF-α and IL-6 were significantly higher in MDD patients than controls. Age, samples source and ethnic origins may play a potential role in heterogeneity.
Assuntos
Transtorno Depressivo Maior/sangue , Adolescente , Adulto , Idoso , Criança , Citocinas/sangue , Transtorno Depressivo Maior/imunologia , Feminino , Humanos , Interleucina-6/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-2/análise , Receptores de Interleucina-2/sangue , Fator de Necrose Tumoral alfa/análise , Adulto JovemRESUMO
Neurosarcoidosis (NS) represents an important differential diagnosis of multiple sclerosis (MS). However, thus far no reliable laboratory marker of neurosarcoidosis exists. The objective of this study was to evaluate whether cerebrospinal fluid (CSF) levels of soluble interleukin 2 receptor (sIL2-R) distinguish NS and other inflammatory disorders of the central nervous system. For this purpose, 139 paired CSF and serum samples from 11 patients with NS, 21 with MS, 10 with CNS vasculitis, 22 with bacterial meningitis, 17 with viral meningitis/encephalitis, seven with neurotuberculosis, and 18 healthy donors were assessed for sIL2-R using an enzyme-linked immunosorbent assay. We found that sIL2-R CSF levels above 150 pg/ml identified untreated NS patients with an overall accuracy of 93% against a group of non-infectious CNS-diseases. Furthermore, an increase in sIL2-R in the CSF was associated with and preceded the outbreak of new neurological symptoms. In conclusion, these findings suggest that sIL2-R measurement in the CSF may be a valuable tool in the diagnosis and follow-up of patients with suspected and proven neurosarcoidosis.
Assuntos
Biomarcadores/líquido cefalorraquidiano , Receptores de Interleucina-2/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/diagnóstico , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Meningite Viral/líquido cefalorraquidiano , Meningite Viral/diagnóstico , Pessoa de Meia-Idade , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Receptores de Interleucina-2/metabolismo , Sarcoidose/líquido cefalorraquidiano , Sarcoidose/diagnóstico , Sensibilidade e Especificidade , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/diagnóstico , Vasculite do Sistema Nervoso Central/líquido cefalorraquidiano , Vasculite do Sistema Nervoso Central/diagnóstico , Adulto JovemRESUMO
Cushing's syndrome is characterized by excessive elevation of glucocorticoid concentrations. In rare cases, the treatment of Cushing's syndrome may result in unmasking or aggravation of diseases responsive to glucocorticoid medication. We report two cases of sarcoidosis following Cushing's syndrome. A 43 year-old male developed cutaneous sarcoidosis and mediastinal lymphadenopathy after resection of an ACTH-secreting pituitary microadenoma. A 32 year-old female showed cutaneous sarcoidosis, arthralgia, mediastinal lymphadenopathy and elevation of angiotensin-converting enzyme and interleukin 2-receptor concentrations after traumatic adrenal bleeding, which ceased formerly undiagnosed hypercortisolism caused by an adrenal adenoma. Sarcoidosis seems to be a rare sequel following the treatment of hypercortisolism. Skin affections were present and suggestive for the diagnosis in all reported cases. As some cases are probably missed when skin affections are lacking, a more frequent evaluation of patients after Cushing's syndrome for the possible diagnosis of sarcoidosis might be necessary.
Assuntos
Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/cirurgia , Síndrome de Cushing/cirurgia , Sarcoidose/etiologia , Dermatopatias/etiologia , Adulto , Artralgia/diagnóstico , Artralgia/etiologia , Feminino , Humanos , Doenças Linfáticas/diagnóstico , Doenças Linfáticas/etiologia , Masculino , Doenças do Mediastino/diagnóstico , Doenças do Mediastino/etiologia , Peptidil Dipeptidase A/análise , Receptores de Interleucina-2/análise , Sarcoidose/diagnóstico , Dermatopatias/diagnósticoRESUMO
We describe for the first time fluorescent virus-like particles decorated with biologically active mono- and multisubunit immune receptors of choice and the basic application of such fluorosomes (FSs) to visualize and target immune receptor-ligand interactions. For that purpose, human embryonic kidney (HEK)-293 cells were stably transfected with Moloney murine leukemia virus (MoMLV) matrix protein (MA) GFP fusion constructs. To produce FSs, interleukins (ILs), IL-receptors (IL-Rs), and costimulatory molecules were fused to the glycosyl phosphatidyl inositol anchor acceptor sequence of CD16b and coexpressed along with MoMLV group-specific antigen-polymerase (gag-pol) in MA::GFP(+) HEK-293 cells. We show that IL-2 decorated but not control-decorated FSs specifically identify normal and malignant IL-2 receptor-positive (IL-2R(+)) lymphocytes by flow cytometry. In addition to cytokines and costimulatory molecules, FSs were also successfully decorated with the heterotrimeric IL-2Rs, allowing identification of IL-2(+) target cells. Specificity of binding was proven by complete inhibition with nonlabeled, soluble ligands. Moreover, IL-2R FSs efficiently neutralized soluble IL-2 and thus induced unresponsiveness of T cells receiving full activation stimuli via T-cell antigen receptor and CD28. FSs are technically simple, multivalent tools for assessing and blocking mono- and multisubunit immune receptor-ligand interactions with natural constituents in a plasma membrane context.