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1.
Viruses ; 14(4)2022 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-35458517

RESUMO

Risk stratification of coronavirus disease-19 (COVID-19) patients by simple markers is critical to guide treatment. We studied the predictive value of soluble interleukin-2 receptor (sIL-2R) for the early identification of patients at risk of developing severe clinical outcomes. sIL-2R levels were measured in 197 patients (60.9% males; median age 61 years; moderate disease, n = 65; severe, n = 132, intubated and/or died, n = 42). All patients received combined immunotherapies (anakinra ± corticosteroids ± intravenous immunoglobulin ± tocilizumab) according to our local treatment algorithm. The endpoint was the composite event of intubation due to severe respiratory failure (SRF) or mortality. Median (interquartile range) sIL-2R levels were significantly higher in patients with severe disease, compared with those with moderate disease (6 (6.2) vs. 5.2 (3.4) ng/mL, p = 0.017). sIL-2R was the strongest laboratory predictive factor for intubation/death (hazard ratio 1.749, 95%CI 1.041-2.939, p = 0.035) after adjustment for other known risk factors. Youden's index revealed optimal sIL-2R cut-off for predicting intubation/death at 9 ng/mL (sensitivity: 67%; specificity: 86%; positive and negative predictive value: 57% and 91%, respectively). Delta sIL-2R between the day of event or discharge minus admission date was higher in patients that intubated/died than in those who did not experience an event (2.91 (10.42) vs. 0.44 (2.88) ng/mL; p = 0.08)). sIL-2R on admission and its dynamic changes during follow-up may reflect disease severity and predict the development of SRF and mortality.


Assuntos
COVID-19 , Receptores de Interleucina-2 , Insuficiência Respiratória , Biomarcadores , COVID-19/metabolismo , COVID-19/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptores de Interleucina-2/sangue , Receptores de Interleucina-2/metabolismo , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/metabolismo
2.
J Psychiatr Res ; 149: 260-264, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35303615

RESUMO

Alterations in the immune system have been associated with a variety of mental illnesses. An increase in circulating inflammatory cytokines is observed not only in people with mental disorders but also in their first-degree relatives. A considerable amount of data support the link between immune system activation and panic disorder (PD) pathogenesis, while it is still unclear whether differential immunological reactivity represents a propensity, a measure of disease activity, or both. To better understand the role of cytokines in PD pathophysiology, we compared the levels of serum inflammatory biomarkers interleukin (IL)-1B and IL-2R among PD patients, offspring of PD patients and healthy controls. The offspring of PD patients were evaluated by a psychiatrist and were considered unaffected by any mental disorder at the time of the evaluation. Concentrations of the cytokines IL-1B and IL-2R were assessed using the Immulite System (Diagnostic Products Corporation). The levels of proinflammatory markers IL-1B and IL-2R were increased in PD patients compared to those of controls, but offspring of PD patients and healthy controls demonstrated no differences regarding peripheral interleukin levels. Our findings suggest that interleukins might represent a disease-dependent marker in PD.


Assuntos
Interleucina-1beta/sangue , Transtorno de Pânico , Receptores de Interleucina-2/sangue , Biomarcadores , Estudos Transversais , Citocinas , Humanos , Interleucinas , Transtorno de Pânico/complicações
3.
Anticancer Res ; 42(3): 1447-1453, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220238

RESUMO

BACKGROUND/AIM: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. High serum levels of soluble IL-2 receptor (sIL-2R) have been reported in acute inflammations and metastatic cancers. This study evaluated the potential of high/increasing sIL-2R levels in predicting metastases. PATIENTS AND METHODS: The study included a total of 1,546 sera samples of subjects from three groups: 119 healthy controls (73 subjects), 566 UM 10 year (10y) disease-free (DF) (220 patients), 861 metastatic UM (268 patients). Patients were followed-up biannually with liver ultrasound and liver function tests for the presence of metastases (Mets). Blood samples to measure the levels of sIL-2R were obtained at the time of primary diagnosis, soon after initial treatment (enucleation, brachytherapy), every 6 months, 10 years from diagnosis, at Mets confirmation by CT, and after additional treatments. RESULTS: Significantly higher sIL-2R levels were detected in the Mets patients compared to healthy controls and 10y DF patients. Compared to the upper limit of the normal levels of sIL-2R, 1,000 U/ml, its levels in metastatic UM were 61%, 25% in 10y DF UM, and 6.25% in the controls. High levels of sIL-2R in metastatic patients, decreased significantly post treatments. Individual kinetics of markers, indicated similar trends of sIL-2R compared to osteopontin and S-Protein 100, predicting metastases, which were confirmed on liver imaging. CONCLUSION: Significantly higher sIL-2R levels were evident in all UM patients with Mets. Significant increases in sIL-2R levels on serial evaluations indicated and predicted UM Mets, enabling earlier treatment of Mets, to improve survival.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Hepáticas/sangue , Melanoma/sangue , Receptores de Interleucina-2/sangue , Neoplasias Uveais/sangue , Estudos de Casos e Controles , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Melanoma/imunologia , Melanoma/secundário , Melanoma/terapia , Valor Preditivo dos Testes , Prognóstico , Fatores de Tempo , Regulação para Cima , Neoplasias Uveais/imunologia , Neoplasias Uveais/patologia , Neoplasias Uveais/terapia
4.
Front Public Health ; 9: 778340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970527

RESUMO

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, and the WHO declared it a pandemic on March 11, 2020. Clinical characteristics and epidemiology features of patients infected with SARS-CoV-2 have been explored in the previous study. However, little is known about the combinative association of liver dysfunction and abnormal interleukins (ILs) in severe patients with COVID-19. This study was designed to estimate whether liver dysfunction and abnormal ILs could predict the severity of COVID-19. This study integrated liver function data and ILs data in patients with COVID-19 and found that liver injury and two ILs, interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6), were closely related to the prognosis of patients with COVID-19. This study may give more exact information to clinicians about the prognosis of patients with COVID-19. In addition, this correlational study between liver disorder and ILs may provide a new vision to diagnosis and treatment in patients.


Assuntos
COVID-19 , Interleucina-6 , Fígado/patologia , Receptores de Interleucina-2/sangue , COVID-19/diagnóstico , Humanos , Interleucina-6/sangue , Pandemias
5.
Front Immunol ; 12: 741268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745113

RESUMO

Objective: We aimed to evaluate the diagnostic value of soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), and combined detection for sepsis infection in patients with closed abdominal injury complicated with severe multiple abdominal injuries. Patients and Methods: One hundred forty patients with closed abdominal injury complicated with severe multiple abdominal injuries who were diagnosed and treated from 2015 to 2020 were divided into a sepsis group (n = 70) and an infection group (n = 70). Results: The levels of sIL-2R, TNF-α, and PCT in the sepsis group were higher than those in the infection group (p < 0.05). The receiver operating characteristic (ROC) curve showed that the areas under the ROC curve (AUCs) of sIL-2R, TNF-α, PCT and sIL-2R+TNF-a+PCT were 0.827, 0.781, 0.821, and 0.846, respectively, which were higher than those of white blood cells (WBC, 0.712), C-reactive protein (CRP, 0.766), serum amyloid A (SAA, 0.666), and IL-6 (0.735). The AUC of the three combined tests was higher than that of TNF-α, and the difference was statistically significant (p < 0.05). There was no significant difference in the AUCs of sIL-2R and TNF-α, sIL-2R and PCT, TNF-α and PCT, the three combined tests and sIL-2R, and the three combined tests and PCT (p > 0.05). When the median was used as the cut point, the corrected sIL-2R, TNF-α, and PCT of the high-level group were not better than those of the low-level group (p > 0.05). When the four groups were classified by using quantile as the cut point, the OR risk values of high levels of TNF-α and PCT (Q4) and the low level of PCT (Q1) after correction were 7.991 and 21.76, respectively, with statistical significance (p < 0.05). Conclusions: The detection of sIL-2R, TNF-α, and PCT has good value in the diagnosis of sepsis infection in patients with closed abdominal injury complicated with severe multiple abdominal injuries. The high concentrations of PCT and TNF-α can be used as predictors of the risk of septic infection.


Assuntos
Traumatismos Abdominais/diagnóstico , Traumatismo Múltiplo/diagnóstico , Pró-Calcitonina/sangue , Receptores de Interleucina-2/sangue , Sepse/diagnóstico , Fator de Necrose Tumoral alfa/sangue , Traumatismos Abdominais/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/complicações , Valor Preditivo dos Testes , Prognóstico , Risco , Sepse/etiologia
6.
Ann Palliat Med ; 10(10): 10938-10945, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763456

RESUMO

BACKGROUND: To analyze the relationship between the peripheral blood absolute lymphocyte count (ALC)/absolute monocyte count (AMC) ratio, soluble interleukin 2 receptor (sIL-2R) level, serum programmed cell death 1 (PD-1) level, and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 78 patients with DLBCL admitted to hospital and 30 healthy controls were enrolled as the case group and control group between August 2019 and June 2020, respectively. The ALC/AMC ratio and the levels of sIL-2R and serum PD-1 between the 2 groups and among patients with different prognoses were compared. The evaluation efficiency of these 3 factors for the prognosis of DLBCL patients was analyzed by receiver operating characteristic (ROC) curves. The risk factors affecting the 1-year survival rate were analyzed by the Cox hazard model. RESULTS: The levels of sIL-2R, AMC, and PD-1 in the case group were significantly higher than those in the control group, while the ALC/AMC ratio was lower than that in the control group (P<0.05). The levels of sIL-2R and PD-1 in the poor prognosis group were significantly higher than those in the good prognosis group, while the ALC/AMC ratio was lower than that in the good prognosis group (P<0.05). The areas under the ROC curve (AUCs) of sIL-2R level, serum PD-1 level, and the ALC/AMC ratio in evaluating the prognosis of DLBCL patients were 0.805 (95% CI: 0.700-0.886), 0.825 (95% CI: 0.722-0.902), 0.792 (95% CI: 0.685-0.876), respectively. The critical values were 474.80 µg/L, 206.85 pg/mL and 3.01, respectively. The differences in the 1-year survival rate among DLBCL patients with different tumor sizes, B symptoms, sIL-2R levels, and ALC/AMC ratios were statistically significant (P<0.05). B symptoms (RR =1.721) and ALC/AMC ratio lower than 3.01 (RR =1.484) were independent influencing factors of the 1-year survival rate in DLBCL patients (P<0.05). CONCLUSIONS: The ALC/AMC ratio, sIL-2R level, and serum PD-1 level can effectively assess the prognosis of DLBCL patients. B symptoms and ALC/AMC ratio lower than 3.01 are risk factors affecting the 1-year survival rate of patients.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico , Monócitos , Receptor de Morte Celular Programada 1/sangue , Receptores de Interleucina-2/sangue , Humanos , Contagem de Linfócitos , Linfócitos , Linfoma Difuso de Grandes Células B/sangue , Prognóstico , Estudos Retrospectivos
7.
Front Immunol ; 12: 750114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691064

RESUMO

Background: Interleukin (IL)-18 is markedly elevated in systemic inflammatory diseases that cause the 'cytokine storm' such as adult-onset Still's disease (AOSD) and hemophagocytic lymphohistiocytosis (HLH). The differences in IL-18 between AOSD and HLH, especially in adults, is uncertain. Macrophage activation syndrome (MAS), a form of secondary HLH, is often difficult to differentiate cases of AOSD that include MAS from other secondary HLH. In this case-control study, we investigated whether serum IL-18 levels could be a useful biomarker for the differential diagnosis of AOSD with or without MAS (AOSD group) and other secondary HLH in adults (adult HLH group). Patients and Methods: We enrolled 46 patients diagnosed with AOSD including 9 patients with MAS and 31 patients in the adult HLH group, which excluded AOSD-associated MAS. The clinical features and laboratory data were compared between the AOSD and adult HLH groups. In addition, we subdivided the AOSD group (with or without MAS) and the adult HLH group (whether lymphoma-associated or not) and compared the four groups. A logistic regression analysis was used to identify factors with high efficacy in differentiating the two groups, followed by a receiver operating characteristic (ROC) curve analysis to evaluate the differential diagnostic ability of IL-18. We analyzed the correlation between IL-18 and various laboratory parameters in the AOSD group. Results: Serum IL-18 levels of patients in the AOSD groups were significantly higher than those of the adult HLH groups, and were closely correlated with ferritin, soluble interleukin-2 receptor (sIL-2R), and other laboratory data. Univariate and multivariate logistic regression analyses revealed that IL-18, sIL-2R, and 'arthralgia or arthritis' are independent factors useful in the differential diagnosis of AOSD from adult HLH. In the differential diagnosis of both groups, the area under the curve obtained from the ROC curve of IL-18 with a cutoff value of 18,550 pg/mL was 0.91 (95% confidence interval 0.83-1.00; sensitivity 90.3%, specificity 93.5%), and the differential diagnosis ability of IL-18 was superior to that of other laboratory data. Conclusions: IL-18 could be a useful biomarker for the differential diagnosis of AOSD and adult HLH.


Assuntos
Interleucina-18/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Síndrome de Ativação Macrofágica/diagnóstico , Doença de Still de Início Tardio/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Diagnóstico Diferencial , Feminino , Ferritinas/sangue , Humanos , Interleucina-18/imunologia , Interleucina-6/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/imunologia , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-2/sangue , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/imunologia
8.
J Cell Biochem ; 122(10): 1350-1359, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34143519

RESUMO

The limitations in discriminating preablation disease-active status of differentiated thyroid carcinoma (DTC) still represent a major challenge to radioiodine dose management. Cytokines, the small protein signaling molecules that constitute the thyroid tumor microenvironment, play significant roles in the facilitation of intercellular communication and the control of tumorigenesis. Also, more attention should be paid to the molecular events within the innate and adaptive immune systems that occur after the organism being exposed to ionizing radiation. Therefore, we implemented a study of 260 patients with DTC in thyroid hormone withdrawal status who were treated with total thyroidectomy to explore the relationship between cytokines and recurrence/active disease status. Besides, we made a cross-sectional study to analyze pre- and post-ablation serum concentration of cytokines of 86 patients with DTC. There was a relationship between clinicohistopathological characteristics of patients with DTC and the presence of cytokines. It is noteworthy that patients with recurrence/active disease were at a higher serum interleukin-2 receptor (IL-2R) level than the disease-free patients (213.59 ± 75.43 pg/ml vs. 186.80 ± 77.40 pg/ml, P = 0.005). Positive correlation was observed between serum IL-2R and thyroglobulin (Tg) (P = 0.003). We also found significant changes in the cytokine profile after radioiodine ablation, including the decrease of tumor necrosis factor-α and IL-8 (P < 0.001, P < 0.001, respectively), and increase of IL-2R (P < 0.001). Thus, we suggest that serum IL-2R may assist in evaluating the disease status during the post-thyroidectomy follow-up and radioiodine therapy has an immunoregulatory effect on serum cytokines.


Assuntos
Biomarcadores Tumorais/sangue , Citocinas/sangue , Radioisótopos do Iodo/uso terapêutico , Recidiva Local de Neoplasia/patologia , Receptores de Interleucina-2/sangue , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Estudos Transversais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/terapia
9.
Cancer Sci ; 112(7): 2642-2651, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33932067

RESUMO

The efficacy and side effects of the second-time humanized CD19 chimeric antigen receptor (CD19-CAR) T-cell therapy after unsuccessful first-time anti-CD19-CAR T-cell therapy and subsequent ibrutinib salvage treatment were observed in patients with refractory B-cell lymphoma. In our study, 3 patients with refractory mantle cell lymphoma (MCL) and 4 patients with refractory follicular lymphoma (FL) reached stable disease (SD), partial remission (PR), or progression of disease (PD) after first-time humanized anti-CD19-CAR T-cell therapy. They received ibrutinib as a salvage treatment and kept an SD in the following 7-16 mo, but their disease progressed again during ibrutinib salvage treatment. All 7 patients received a second-time humanized anti-CD19-CAR T-cell therapy, which was the same as their first-time anti-CD19-CAR T-cell therapy. In total, 3 MCL patients and 3 FL patients reached complete response (CR) with the second-time anti-CD19-CAR T-cell therapy combined with ibrutinib, whereas 1 FL patient reached PR. There were no differences in the transduction efficiency and proliferation between the 2 instances of anti-CD19-CAR T-cell therapy. However, the second-time anti-CD19-CAR T-cell therapy led to higher peaks of anti-CD19-CAR T cells and anti-CD19-CAR gene copies, but also to higher grades of cytokine release syndrome (CRS) and more serious hematological toxicity. The successful outcome of the second-time anti-CD19-CAR T-cell therapy might suggest that the previous ibrutinib treatment improved the activities of anti-CD19-CAR T cells.


Assuntos
Adenina/análogos & derivados , Imunoterapia Adotiva/métodos , Linfoma Folicular/terapia , Linfoma de Célula do Manto/terapia , Piperidinas/uso terapêutico , Receptores de Antígenos Quiméricos , Terapia de Salvação , Adenina/uso terapêutico , Adulto , Idoso , Terapia Combinada/métodos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Interleucina-6/sangue , Interleucina-8/sangue , Linfoma de Células B/sangue , Linfoma de Células B/terapia , Linfoma Folicular/sangue , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/terapia , Linfoma de Célula do Manto/sangue , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos Quiméricos/genética , Receptores de Interleucina-2/sangue , Indução de Remissão/métodos , Retratamento , Resultado do Tratamento
10.
Arq. bras. med. vet. zootec. (Online) ; 73(3): 747-751, May-June 2021. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1278348

RESUMO

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/veterinária
11.
Int J Hematol ; 114(2): 217-221, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33847924

RESUMO

High pre-treatment serum soluble interleukin-2 receptor (sIL-2R) levels are associated with poor overall survival (OS) of patients with newly diagnosed follicular lymphoma (FL). We evaluated the usefulness of pre-treatment sIL-2R levels in selecting a treatment regimen for advanced-stage FL with low tumor burden (FL-LTB). This retrospective, multicenter observational study enrolled consecutive patients who received a rituximab-containing regimen for newly diagnosed advanced stage FL-LTB (grade 1-3a) between 2008 and 2018. We applied a previously reported cut-off value of 1800 IU/mL for sIL-2R. A total of 211 patients were eligible for the analysis. Among patients with high sIL-2R (47 patients, 22.3%), the OS rates for patients treated by rituximab monotherapy (R-mono) (11 patients) were significantly lower than those treated by rituximab-combination chemotherapy (R-chemo) (36 patients): 5-year OS rates were 66.7% and 94.4%, respectively (P = 0.007). Among patients with low sIL-2R (164 patients, 77.7%), OS rates were comparably good between the R-mono group (34 patients) and the R-chemo group (130 patients): 5-year OS rates were 100% and 98.3%, respectively (P = 0.38). Our results suggest that R-chemo may yield better OS than R-mono for patients with newly diagnosed advanced-stage FL-LTB and high pre-treatment serum sIL-2R levels.


Assuntos
Biomarcadores Tumorais , Linfoma Folicular/sangue , Linfoma Folicular/diagnóstico , Receptores de Interleucina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tomada de Decisão Clínica , Gerenciamento Clínico , Feminino , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral
12.
Infez Med ; 29(1): 1-9, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33664168

RESUMO

In this review, we summarize the possible mechanisms of COVID-19-associated coagulopathy and compare its features to other similar conditions. The recent COVID-19 pandemic has caused enormous mortality and morbidity worldwide. It is important to note that COVID-19-associated thrombotic events play a huge role in the morbidity of this disease. Interestingly, it has been observed that this complication may occur despite prophylactic anticoagulant therapy. Recent studies on COVID-19-associated coagulopathy revealed that the COVID-19-associated hypercoagulability is more frequently observed among those with a severe course of the disease. Various mechanisms have been suggested as explanations for this condition and possible underlying etiologies.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , COVID-19/complicações , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/metabolismo , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/metabolismo , COVID-19/sangue , Endotélio Vascular/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemostasia , Heparina/efeitos adversos , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Receptores de Interleucina-2/sangue , SARS-CoV-2/patogenicidade , Trombofilia/etiologia , Trombose/etiologia , Fator de Necrose Tumoral alfa/sangue , Internalização do Vírus
13.
Front Immunol ; 12: 626235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33584733

RESUMO

Objectives: The coordinated immune response of the host is the key of the successful combat of the body against SARS-CoV-2 infection and is decisive for the development and progression of COVID-19. In this study, we aimed to investigate whether the immunological phenotype of patients are associated with duration of illness in patients with severe COVID-19. Method: In this single-center study, 69 patients with severe or critical COVID-19 were recruited retrospectively. Immunological parameters including counts of white blood cells, neutrophils, lymphocytes, the neutrophil-to-lymphocyte ratio, and levels of circulating cytokines and cytokine receptors were screened for their association with disease severity, survival and duration of illness of COVID-19. Results: Our data confirmed previous results that neutrophil-to-lymphocyte ratio and circulating levels of IL-6 represent prominent biomarker for the prediction of disease severity and survival of COVID-19. However, this study shows for the first time that duration of illness in patients with severe COVID-19 is positively associated with serum levels of IL-8 (P=0.004) and soluble IL-2Rα (P=0.025). Conclusion: The significant association of duration of illness with circulating levels of IL-8 and soluble IL-2Rα in patients with severe COVID-19 implicates that neutrophils and T cells are involved in the evolution of COVID-19.


Assuntos
COVID-19/sangue , Interleucina-8/sangue , Receptores de Interleucina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/imunologia , Citocinas/sangue , Citocinas/imunologia , Feminino , Humanos , Interleucina-8/imunologia , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Receptores de Interleucina-2/imunologia , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
14.
Anticancer Res ; 41(2): 1021-1026, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517310

RESUMO

BACKGROUND/AIM: Biomarkers for immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) are required. We encountered a patient whose skin irAE fluctuated in parallel with serum soluble interleukin-2 receptor (sIL-2R). PATIENTS AND METHODS: We examined 15 patients with cancer who received ICIs. Serum sIL-2R levels before and during ICI treatment were measured. The sIL-2R levels of preserved serum samples from another five patients who developed grade 3 irAEs were measured. RESULTS: Twelve patients showed no significant changes in sIL-2R levels during ICI treatment. Baseline serum sIL-2R levels in three patients increased beyond the normal range before the second cycle. These three patients had grade ≥2 irAEs at the second cycle treatment visit, supporting our hypothesis. Furthermore, at diagnosis of irAEs, the sIL-2R levels of all preserved samples from patients with grade 3 irAEs were significantly elevated. CONCLUSION: Serum sIL-2R is a promising biomarker for the diagnosis of irAEs.


Assuntos
Biomarcadores Tumorais/sangue , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Receptores de Interleucina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Resultado do Tratamento , Regulação para Cima
18.
J Breath Res ; 15(1): 016016, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33336649

RESUMO

INTRODUCTION: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is an urgent need to identify new and novel biomarkers to help differentiate between clinical phenotypes and guide clinical decisions with respect to commencing and monitoring treatment. Across the spectrum of respiratory disease there has been a growing interest in the role of breath-based biomarkers given their non-invasive nature and ability to repeat sampling with ease for serial monitoring. Soluble interleukin-2 receptor (sIL2R) in bronchoalveolar lavage and serum correlates with disease activity in sarcoidosis; however, no previous study has evaluated sIL2R in exhaled breath. OBJECTIVES: The main aim of this cross-sectional case-controlled pilot study was to determine the concentration of sIL2R in exhaled breath condensate (EBC) from patients with recently diagnosed sarcoidosis compared to healthy volunteers and to establish, if present, if this correlated with markers of disease activity, pulmonary function tests and serological markers used in current clinical practice. METHODS: Paired serum and EBC samples were collected from twelve treatment naïve patients with histologically proven sarcoidosis diagnosed during the previous six months and compared to twelve healthy volunteers matched for age and gender. RESULTS: Mean concentration of serum sIL2R was significantly elevated in participants with sarcoidosis compared to healthy controls (1584.3 ± 489.1 versus 874.2 ± 235.7 pg mL-1; p = 0.001). Soluble interleukin-2 receptor in EBC was detectable in only five subjects including three participants with sarcoidosis. The range of sIL2R across all five samples was 148.0-288.2 pg mL-1 with the two highest concentrations observed in two participants with sarcoidosis. There was no significant difference observed in EBC sIL2R between sarcoidosis and healthy controls (p = 0.71). No apparent correlations were observed between EBC sIL2R and radiological stage, pulmonary function tests or serological markers. CONCLUSION: Soluble interleukin-2 receptor is detectable in EBC; however, the findings from our study do not support its role as a diagnostic marker in sarcoidosis. Further research is required to evaluate its prognostic utility.


Assuntos
Testes Respiratórios , Expiração , Receptores de Interleucina-2/metabolismo , Sarcoidose Pulmonar/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Receptores de Interleucina-2/sangue , Reprodutibilidade dos Testes , Sarcoidose Pulmonar/sangue , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/fisiopatologia , Solubilidade
19.
Mediators Inflamm ; 2020: 6259064, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061828

RESUMO

Previously, we showed that serum soluble interleukin-2 receptor (sIL-2R) levels, a marker for T-cell activation, were higher in complex regional pain syndrome (CRPS) patients than in healthy controls, suggesting pathogenic T-cell activation in CRPS. Additionally, sIL-2R levels discriminated well between CRPS and healthy controls with a high sensitivity (90%) and specificity (89.5%), suggesting a possible role for sIL-2R in the diagnosis of CRPS. In order to further validate this marker in the diagnostic workup of CRPS, we conducted this prospective cohort study in which we determined sIL-2R levels in patients that were referred to our tertiary referral center with a suspicion of CRPS in a limb, and subsequently compared sIL-2R levels between the patients that were diagnosed with CRPS (CRPS group) and those who were not (no CRPS group). A group of anonymous blood bank donors were used as a healthy control group. Furthermore, we explored the relationship between sIL-2R and CRPS disease severity using the CRPS severity score. Median sIL-2R levels of both the CRPS group (2809.0 pg/ml; Q3-Q1: 3913.0-1589.0) and no CRPS group (3654.0 pg/ml; Q3-Q1: 4429.0-2095.5) were significantly higher than that of the control group (1515.0 pg/ml; Q3-Q1: 1880.0-1150.0): CRPS vs. controls, p < .001; no CRPS vs. controls, p < 0.001. Serum sIL-2R levels did not differ significantly between the CRPS and no CRPS group. A statistically significant negative correlation was observed between sIL-2R levels and the CRPS severity score (r s = -0.468, p = 0.024). Our results confirm our previous findings of higher sIL-2R levels in CRPS patients than in healthy controls. We further showed that serum sIL-2R cannot differentiate between CRPS and other pain conditions of a limb in a tertiary referral setting. Interestingly, a negative correlation was found between sIL-2R and CRPS disease severity; this finding warrants further research into the relationship between sIL-2R and CRPS disease severity.


Assuntos
Biomarcadores/sangue , Síndromes da Dor Regional Complexa/sangue , Dor/sangue , Receptores de Interleucina-2/sangue , Adulto , Síndromes da Dor Regional Complexa/diagnóstico , Feminino , Humanos , Ativação Linfocitária/fisiologia , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Estudos Prospectivos
20.
Artigo em Inglês | MEDLINE | ID: mdl-33093764

RESUMO

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widely available diagnostic tool for suspected stage I/II sarcoidosis. Combination of EBUS-TBNA and transbronchial lung biopsy (TBLB) has been proposed as diagnostic procedure in clinical settings. OBJECTIVES: The aim of this study was to assess the diagnostic yield of combined EBUS-TBNA and TBLB and identify the markers correlated with a high diagnostic rate. METHODS: We retrospectively analyzed the data of 37 patients with suspected stage I/II sarcoidosis with enlarged hilar or mediastinal lymph nodes on computed tomography (CT) images. These patients had been scheduled to undergo EBUS-TBNA and TBLB. Serum levels of sarcoidosis markers (angiotensin-converting enzyme [ACE], soluble interleukin-2 receptor [sIL-2R], and lysozyme), CT findings, and examination techniques were evaluated as predictive markers for diagnosis. RESULTS: Of the 37 patients, 32 had undergone both EBUS-TBNA and TBLB, while the remaining 5 patients had only undergone EBUS-TBNA. The diagnosis was confirmed by TBLB in 16 of the 32 patients (50.0%), EBUS-TBNA in 31 of the 37 patients (83.8%), and combined TBLB and EBUS-TBNA in all patients (100.0%). The serum level of sIL-2R, but not that of ACE or lysozyme, was correlated with successful diagnosis by EBUS-TBNA. CONCLUSION: In patients with stage I/II sarcoidosis, the serum level of sIL-2R is a promising and useful marker for predicting the diagnosis by EBUS-TBNA and reducing the burden of additional TBLB and its possible complications. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 8-16).


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Receptores de Interleucina-2/sangue , Sarcoidose Pulmonar/sangue , Sarcoidose Pulmonar/patologia , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sarcoidose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X
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