RESUMO
BACKGROUND: Kawasaki disease (KD) is a pediatric systemic vasculitis characterized by endothelial cell dysfunction. Semaphorin 7A (Sema7A) has been reported to regulate endothelial phenotypes associated with cardiovascular diseases, while its role in KD remains unknown. This study aims to investigate the effect of Sema7A on endothelial permeability and inflammatory response in KD conditions. METHODS: Blood samples were collected from 68 KD patients and 25 healthy children (HC). The levels of Sema7A and A Disintegrin and Metalloprotease 17 (ADAM17) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and Sema7A expression in blood cells was analyzed by flow cytometry. Ex vivo monocytes were used for Sema7A shedding assays. In vitro human coronary artery endothelial cells (HCAECs) were cultured in KD sera and stimulated with Sema7A, and TNF-α, IL-1ß, IL-6, and IL-18 of HCAECs were measured by ELISA and qRT-PCR. HCAECs monolayer permeability was measured by FITC-dextran. RESULTS: The serum level of Sema7A was significantly higher in KD patients than in HC and correlated with disease severity. Monocytes were identified as one of the source of elevated serum Sema7A, which implicates a process of ADAM17-dependent shedding. Sera from KD patients induced upregulation of plexin C1 and integrin ß1 in HCAECs compared to sera from HC. Sema7A mediated the proinflammatory cytokine production of HCAECs in an integrin ß1-dependent manner, while both plexin C1 and integrin ß1 contributed to Sema7A-induced HCAEC hyperpermeability. CONCLUSIONS: Sema7A is involved in the progression of KD vasculitis by promoting endothelial permeability and inflammation through a plexin C1 and integrin ß1-dependent pathway. Sema7A may serve as a potential biomarker and therapeutic target in the prognosis and treatment of KD.
Assuntos
Antígenos CD , Integrina beta1 , Síndrome de Linfonodos Mucocutâneos , Receptores de Superfície Celular , Semaforinas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Proteína ADAM17/metabolismo , Antígenos CD/metabolismo , Permeabilidade Capilar , Estudos de Casos e Controles , Células Cultivadas , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Proteínas Ligadas por GPI , Inflamação/metabolismo , Integrina beta1/metabolismo , Monócitos/metabolismo , Síndrome de Linfonodos Mucocutâneos/metabolismo , Síndrome de Linfonodos Mucocutâneos/sangue , Proteínas do Tecido Nervoso/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/sangue , Semaforinas/metabolismo , Semaforinas/sangueRESUMO
OBJECTIVE: Semaphorin4D (Sema4D), a novel integral membrane glycoprotein, plays a role in atherosclerosis, angiogenesis and chronic inflammation. Elevated levels of sema4D were presented in myocardial infarction, heart failure and atrial fibrillation. Aim of the study was to investigate the relation between sema4D and recurrence after catheter ablation (CA) in paroxysmal AF. METHODS: The present study included 161 paroxysmal AF patients (PAF) (101 patients undergone CA) and 60 healthy subjects. Serum levels of sema4D were measured and study participants were followed-up for 3 months and 1 year since CA in terms of recurrence respectively. RESULTS: Sema4D levels were significantly elevated in the recurrent group compared to the non-recurrent PAF patients (p < 0.001). Sema4D was importantly positively correlated with both left atrial volume index (r = 0.51, p < 0.013) and high sensitive C-reactive protein (r = 0.38), p < 0.011). In multivariate analysis, sema4D [odds ratio (OR) = 1.23, 95% CI 1.11-1.42; p < 0.001] and left atrial diameter (OR = 1.13, 95% CI 1.02-1.23; p = 0.012) were found to be significant independent risk parameters for recurrence. CONCLUSIONS: Sema4D is a novel biomarker that may help to identify individuals with recurrence after CA procedure in long term period in PAF.
Assuntos
Antígenos CD/sangue , Fibrilação Atrial/cirurgia , Ablação por Cateter , Semaforinas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Adulto JovemRESUMO
OBJECTIVE: Semaphorin 5A (SEMA 5A) is a neuroprotein that regulates the formation of excitatory synapses between neurons, important in autoimmunity, inflammatory processes and behaviors. This study aimed to investigate the SEMA 5A levels in patients with obsessive-compulsive disorder (OCD) diagnosed for the first time and evaluate the relationship of disease and disease severity with the blood SEMA 5A level and hemogram. METHODS: More than 41,465 patients who applied to the psychiatry clinic from January 2018 to December 2020 were evaluated according to the DSM-5 criteria; 57 patients diagnosed with OCD for the first time, who met the inclusion criteria, were included in the study. Disease severity was investigated administering the Yale Brown Obsessive Compulsion Scale. The peripheral blood SEMA 5A level and hemogram were measured and evaluated in relation to platelet (PLT) activity, neutrophil-lymphocyte ratio (NLR), PLT-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), C-reactive protein (CRP), and compared with control group of 26 people. RESULTS: The comparison of the groups revealed a significant difference in SEMA 5A and CRP level, neutrophil count and percentage, lymphocyte count, PLT activity. A significant correlation was found between disease and SEMA 5A level, NLR, PLR, and PLT parameters in diagnosis of OCD. As the severity of OCD increased, the SEMA 5A level and PLT count decreased, while the PDW and MLR values increased. CONCLUSION: In patients with OCD, a relationship was found between plasma SEMA 5A, PLT activity, NLR, PLR, and MLR activity levels with disease and the disease severity.
Assuntos
Transtorno Obsessivo-Compulsivo , Semaforinas , Humanos , Linfócitos , Neutrófilos , Transtorno Obsessivo-Compulsivo/diagnóstico , Semaforinas/sangue , Índice de Gravidade de DoençaRESUMO
CD100 is an immune semaphorin constitutively expressed on T-cells. Matrix metalloproteinase (MMP) is an important mediator of membrane-bound CD100 (mCD100) cleavage to generate soluble CD100 (sCD100), which has immunoregulatory activity in immune cell responses. The aim of the study was to investigate the level and role of sCD100 and mCD100 in modulating CD8+ T-cell function in non-small cell lung cancer (NSCLC). sCD100 and MMP-14 levels in the serum and bronchoalveolar lavage fluid (BALF), and mCD100 expression on peripheral and lung-resident CD8+ T-cells were analysed in NSCLC patients. The ability to induce sCD100 and the effect of MMP-14 on mCD100 shedding for the regulation of non-cytolytic and cytolytic functions of CD8+ T-cells were also analysed in direct and indirect contact co-culture systems. NSCLC patients had lower serum sCD100 and higher mCD100 levels on CD8+ T-cells compared with healthy controls. BALF from the tumour site also had decreased sCD100 and increased mCD100 on CD8+ T-cells compared with the non-tumour site. Recombinant CD100 stimulation enhanced non-cytolytic and cytolytic functions of CD8+ T-cells from NSCLC patients, whereas blockade of CD100 receptor CD72 attenuated CD8+ T-cell activity. NSCLC patients had lower MMP-14 in the serum and in BALF from the tumour site. Recombinant MMP-14 mediated mCD100 shedding from CD8+ T-cell membrane, and led to promotion of CD8+ T-cell response in NSCLC patients. Overall, decreased MMP-14 resulted in insufficient CD100 shedding, leading to suppression of peripheral and lung-resident CD8+ T-cell activity in NSCLC.
Assuntos
Antígenos CD/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Metaloproteinase 14 da Matriz/metabolismo , Semaforinas/metabolismo , Adulto , Idoso , Antígenos CD/sangue , Líquido da Lavagem Broncoalveolar/química , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Técnicas de Cocultura , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Ativação Linfocitária , Masculino , Metaloproteinase 14 da Matriz/sangue , Pessoa de Meia-Idade , Cultura Primária de Células , Proteínas Recombinantes/metabolismo , Semaforinas/sangue , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Evasão Tumoral , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: Sema4A is a regulator of helper T cell (Th) activation and differentiation in the priming phase, which plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). However, the role of Sema4A in the effector phase remains elusive. We aimed to investigate the role of Sema4A at the effector phase in adoptively transferred EAE model. Clinical features and cytokine profiles of MS patients with high Sema4A levels were also examined in detail to clarify the correlation between Sema4A levels and disease activity of patients with MS. METHODS: We adoptively transferred encephalitogenic Th1 or Th17 cells to wild type (WT) or Sema4A-deficient (Sema4A KO) mice and assessed severity of symptoms and cellular infiltration within the central nervous system (CNS). In addition, we analyzed clinical and radiological features (n = 201), levels of serum IFN-γ and IL-17A (n = 86), complete remission ratio by IFN-ß (n = 38) in all of relapsing-remitting multiple sclerosis (RRMS) patients enrolled in this study. RESULTS: Sema4A KO recipient mice receiving Th17-skewed WT myelin oligodendrocyte glycoprotein (MOG)-specific encephalitogenic T cells showed a significant reduction in the clinical score compared to the WT recipient mice. However, Sema4A KO recipient mice showed similar disease activity to the WT recipient mice when transferred with Th1-skewed encephalitogenic T cells. Bone marrow chimeric study indicated that Sema4A expressed on hematopoietic cells, but not the CNS resident cells, are responsible for augmenting Th17-mediated neuroinflammation. Additionally, in contrast to comparable IFN-γ levels, IL-17A is significantly higher in RRMS patients with high Sema4A level than those with low Sema4A patients with high Sema4A levels showed earlier disease onset, more severe disease activity and IFN-ß unresponsiveness than those with low Sema4A levels. CONCLUSIONS: Sema4A is involved not only in the Th cell priming but also in the acceleration of Th17 cell-mediated neuroinflammation in the effector phase, which could contribute to the higher disease activity observed in RRMS patients with high serum Sema4A levels.
Assuntos
Inflamação/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Semaforinas/imunologia , Células Th17/imunologia , Animais , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Semaforinas/sangueRESUMO
A growing body of data suggests that semaphorins are involved in both normal and pathological immune responses, as well as autoimmune pathologies. To investigate the plasma semaphorin 3A (Sema3A) and semaphorin 7A (Sema7A) levels in systemic lupus erythematosus (SLE) patients and their correlation with clinical manifestations and laboratory indexes, a two-step method was applied. First, 80 SLE patients and 80 healthy controls were recruited for comparing serum Sema3A and Sema7A concentrations. Second, 40 rheumatoid arthritis (RA) patients and 40 sjögren's syndrome (SS) patients were then included as disease controls. Plasma Sema3A and Sema7A concentrations were detected by ELISA. There were significant differences in Sema3A and Sema7A among four groups. When compared to healthy controls, both Sema3A and Sema7A levels were decreased in SLE and increased in RA; increased Sema3A level and decreased Sema7A level were found in SS. There were significant differences in Sema3A concentration between SLE and RA, SLE and SS. Moreover, there were significant differences in Sema7A level between SLE and RA, SS and RA. However, no significant differences in Sema3A between SS and RA and no significant differences in Sema7A between SS and SLE were observed. Both plasma Sema3A and Sema7A levels were correlated with anti-SSA and IgM. Area under curve (AUC) of the receiver operating characteristic (ROC) curve for Sema3A and Sema7A were 0.535 (0.455-0.613) and 0.671 (0.594-0.742), respectively. Aberrant Sema3A and Sema7A expression and their clinical associations in SLE suggest their important role in this disease.
Assuntos
Antígenos CD/sangue , Lúpus Eritematoso Sistêmico/sangue , Semaforina-3A/sangue , Semaforinas/sangue , Adulto , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The aim of this study was to detect the expression of long noncoding RNA small nucleolar RNA host gene 18 (SNHG18) andsemaphorin 5A (SEMA5A) genes in multiple myeloma (MM) patients and to explore the correlation of the expression of these genes with the clinical characteristics and prognosis of MM patients. METHODS: Forty-seven newly diagnosed MM, 18 complete remission MM, 13 refractory/relapse MM, and 22 iron deficiency anemia (serving as control) samples were extracted at the Department of Hematology, Second Aï¬liated Hospital of Xian Jiaotong University between January 2015 and December 2016. The clinical features of the MM patients are summarized. Real-time quantitative PCR was performed to analyze the relative expression levels of the SNHG18 and SEMA5Agenes. The clinical characteristics and overall survival (OS) of the MM patients were statistically analyzed while measuring different levels of SNHG18 and SEMA5Agene expression. At the same time, the correlation between the expression of SNHG18 and SEMA5A was also analyzed. RESULTS: The analysis confirmed that SNHG18 and its possible target gene SEMA5A were both highly expressed in newly diagnosed MM patients. After analyzing the clinical signiï¬cance of SNHG18 and SEMA5A in MM patients, we found that the expression of SNHG18 and SEMA5A was related to the Durie-Salmon (DS), International Staging System (ISS), and Revised International Staging System (R-ISS) classification systems, and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART; p < 0.05). Moreover, we observed a significant difference in OS between the SNHG18/SEMA5A high expression group and the low expression group. We found a positive correlation between SNHG18 and SEMA5A expression (r = 0.709, p < 0.01). Surprisingly, the expected median OS times of both the SNHG18 and SEMA5Ahigh expression groups were significantly decreased, which was in contrast to those of both the SNHG18 and SEMA5Alow expression groups and the single-gene high expression group (p < 0.05). CONCLUSION: High expression of both SNHG18 and SEMA5A is associated with poor prognosis in patients with MM.
Assuntos
Regulação Neoplásica da Expressão Gênica , Mieloma Múltiplo/sangue , Proteínas de Neoplasias/sangue , RNA Longo não Codificante/sangue , RNA Neoplásico/sangue , Semaforinas/sangue , Adulto , Idoso , Anemia Ferropriva/sangue , Anemia Ferropriva/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Prognóstico , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Reação em Cadeia da Polimerase em Tempo Real , Recidiva , Indução de Remissão , Semaforinas/biossíntese , Semaforinas/genéticaRESUMO
Atherosclerosis is the underlying pathology in a major part of cardiovascular disease, the leading cause of mortality in developed countries. The infiltration of monocytes into the vessel walls of large arteries is a key denominator of atherogenesis, making monocytes accountable for the development of atherosclerosis. With the development of high-throughput transcriptome profiling platforms and cytometric methods for circulating cells, it is now feasible to study in-depth the predicted functional change of circulating monocytes reflected by changes of gene expression in certain pathways and correlate the changes to disease outcome. Neuroimmune guidance cues comprise a group of circulating- and cell membrane-associated signaling proteins that are progressively involved in monocyte functions. Here, we employed the CIRCULATING CELLS study cohort to classify cardiovascular disease patients and healthy individuals in relation to their expression of neuroimmune guidance cues in circulating monocytes. To cope with the complexity of human datasets featured by noisy data, nonlinearity and multidimensionality, we assessed various machine-learning methods. Of these, the linear discriminant analysis, Naïve Bayesian model and stochastic gradient boost model yielded perfect or near-perfect sensibility and specificity and revealed that expression levels of the neuroimmune guidance cues SEMA6B, SEMA6D and EPHA2 in circulating monocytes were of predictive values for cardiovascular disease outcome.
Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Efrinas/sangue , Aprendizado de Máquina , Monócitos/metabolismo , Netrina-1/sangue , Semaforinas/sangue , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Estudos de Coortes , Efrinas/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Netrina-1/genética , Semaforinas/genética , TranscriptomaRESUMO
Objective: To explore the correlation between Semaphorin 4D (Sema4D) and rheumatoid arthritis (RA) clinical manifestations, laboratory indexes, bone destruction and rheumatoid arthritis related interstitial lung disease(RA-ILD), and to analyze its significance in evaluating the severity of patients with rheumatoid arthritis. Methods: A total of 108 RA patients and 50 healthy controls from September 2018 to October 2019 were collected from the Department of Rheumatology and Immunology, Peking University People's Hospital and Beijing Haidian Hospital. According to the DAS 28 score, RA patients were divided into active disease group (DAS28>2.6) and stable disease group (DAS28 ≤ 2.6). Fifty healthy controls. The levels of Sema4D in serum were detected by enzyme-linked immunoassay method (ELISA), and their correlation with clinical manifestations of RA, laboratory indicators, degree of bone damage and RA-ILD were analyzed. Results: The level of serum Sema4D in RA active group was significantly higher than that in stable group and healthy control group (P<0.05). The concentration serum Sema4D was positively correlated with C-reactive protein(CRP) (r=0.28, P<0.05), rheumatoid factor(RF) (r=0.25, P<0.05) and the 28-joint disease activity score (DAS28) (r=0.45, P<0.01). The concentration serum Sema4D was positively correlated with ß-Crosslaps(r=0.20, P<0.05) and Sharp-van der Heijde score (SHS)(r=0.13, P<0.05). The concentration serum Sema4D was positively correlated with Vascular endothelial growth factor (VEGF)(r=0.25, P<0.05) and Warrick score of chest CT in RA patients(r=0.27, P<0.05). The anti-cyclic citrullinated peptid(CCP) antibody, DAS28, VEGF and the incidence of RA-ILD were significantly higher than that in Sema4D negative group (P<0.05). Conclusions: Serum Sema4D level in RA patients is closely related to the disease activity, bone destruction and RA-ILD. Serum Sema4D can be used as an indicator of disease monitoring and prognosis evaluation in RA patients.
Assuntos
Artrite Reumatoide , Doenças Pulmonares Intersticiais , Semaforinas/sangue , Biomarcadores , Humanos , Peptídeos Cíclicos , Fator Reumatoide , Fator A de Crescimento do Endotélio VascularRESUMO
Semaphorin 7A (Sema7A), a neural guidance cue, was recently identified to regulate atherosclerosis in mice. However, the clinical relevance of Sema7A with atherosclerotic diseases remains unknown. The aim of this study was to investigate the association between serum Sema7A and the risk of acute atherothrombotic stroke (AAS). We measured serum concentrations of Sema7A in 105 newly onset AAS cases and 105 age- and sex-matched controls, showing that median Sema7A level in AAS cases was over three times of that in controls (5.86 vs 1.66 ng/mL). Adjusted for hypertension, body mass index, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, current smoking and alcohol consumption, multivariate logistic regression showed that higher Sema7A was independently associated with the odds of AAS (OR = 6.40, 95% CI: 2.88-14.25). Each 1-standard deviation increase in Sema7A was associated with a threefold higher odds of AAS (OR = 3.42, 95% CI: 1.84-6.35). Importantly, adding Sema7A to a multivariate logistic model containing conventional cardiovascular risk factors improved the area under receiver operating characteristic curves from 0.831 to 0.891 for the association with AAS. In conclusion, elevated serum Sema7A is independently associated with the risk of AAS, suggesting that it may play a potential role in AAS.
Assuntos
Antígenos CD/sangue , Aterosclerose/diagnóstico , Biomarcadores/sangue , Semaforinas/sangue , Acidente Vascular Cerebral/diagnóstico , Aterosclerose/sangue , Aterosclerose/etiologia , Estudos de Casos e Controles , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Masculino , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND & AIMS: CD100 is constitutively expressed on T cells and can be cleaved from the cell surface by matrix metalloproteases (MMPs) to become soluble CD100 (sCD100). Both membrane-bound CD100 (mCD100) and sCD100 have important immune regulatory functions that promote immune cell activation and responses. This study investigated the expression and role of mCD100 and sCD100 in regulating antiviral immune responses during HBV infection. METHODS: mCD100 expression on T cells, sCD100 levels in the serum, and MMP expression in the liver and serum were analysed in patients with chronic HBV (CHB) and in HBV-replicating mice. The ability of sCD100 to mediate antigen-presenting cell maturation, HBV-specific T cell activation, and HBV clearance were analysed in HBV-replicating mice and patients with CHB. RESULTS: Patients with CHB had higher mCD100 expression on T cells and lower serum sCD100 levels compared with healthy controls. Therapeutic sCD100 treatment resulted in the activation of DCs and liver sinusoidal endothelial cells, enhanced HBV-specific CD8 T cell responses, and accelerated HBV clearance, whereas blockade of its receptor CD72 attenuated the intrahepatic anti-HBV CD8 T cell response. Together with MMP9, MMP2 mediated mCD100 shedding from the T cell surface. Patients with CHB had significantly lower serum MMP2 levels, which positively correlated with serum sCD100 levels, compared with healthy controls. Inhibition of MMP2/9 activity resulted in an attenuated anti-HBV T cell response and delayed HBV clearance in mice. CONCLUSIONS: MMP2/9-mediated sCD100 release has an important role in regulating intrahepatic anti-HBV CD8 T cell responses, thus mediating subsequent viral clearance during HBV infection. LAY SUMMARY: Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. The clearance of HBV relies largely on an effective T cell immune response, which usually becomes dysregulated in chronic HBV infection. Our study provides a new mechanism to elucidate HBV persistence and a new target for developing immunotherapy strategies in patients chronically infected with HBV.
Assuntos
Antígenos CD , Linfócitos T CD8-Positivos/imunologia , Vírus da Hepatite B/fisiologia , Hepatite B Crônica , Imunidade Celular/imunologia , Fígado , Metaloproteinase 2 da Matriz/imunologia , Metaloproteinase 9 da Matriz/imunologia , Semaforinas , Animais , Antígenos CD/sangue , Antígenos CD/imunologia , Perfilação da Expressão Gênica , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Fígado/imunologia , Fígado/virologia , Ativação Linfocitária/imunologia , Camundongos , Semaforinas/sangue , Semaforinas/imunologiaRESUMO
INTRODUCTION: Semaphorin-4D (CD100), generated by CD4/CD8 T-cells and its receptor on B cells - CD72, play a role in immune regulation. Both have soluble forms - sCD100/sCD72. METHODS: sCD100 and sCD72 levels were determined by ELISA (MyBioSource, USA). RESULTS: 28 chronic HIV patients and 50 matched healthy volunteers participated in our study. Before treatment, CD4 T-cells counts were 267⯱â¯216â¯cells/mcl and viral load (VL) was 586,675⯱â¯1897,431â¯copies/ml. Two years following HAART, CD4 T-cells counts rose to 475⯱â¯264â¯cells/mcl and VL dropped to 2050⯱â¯10,539â¯copies/ml. CD8 T-cells counts were stable. sCD72 levels prior (4.13⯱â¯2.03â¯ng/ml) and following HAART (3.53⯱â¯2.01â¯ng/ml) were similar to control levels (4.51⯱â¯2.66â¯ng/ml). sCD100 levels before (40.47⯱â¯31.4â¯ng/ml) and following HAART (37.68⯱â¯29.44â¯ng/ml) were significantly lower compared to controls (99.67⯱â¯36.72â¯ng/ml) despite the significant increase in CD4 T-cells counts. CONCLUSIONS: The permanent low levels of the immunoregulator sCD100 suggest a role for CD100 in the immune dysfunction and T cells exhaustion of HIV.
Assuntos
Antígenos CD/sangue , Infecções por HIV/imunologia , Semaforinas/sangue , Adolescente , Adulto , Antígenos CD/fisiologia , Antígenos de Diferenciação de Linfócitos B/sangue , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Semaforinas/fisiologia , Carga Viral , Adulto JovemRESUMO
Objective: To investigate the clinical significance of soluble Semaphorin 5A(Sema 5A) in patients of rheumatoid arthritis(RA) and the effect of Sema 5A on osteoclastogenesis in RAW264.7 cells. Methods: (1)Soluble Sema 5A was detected in the serum of 62 RA patients, 30 osteoarthritis(OA) patients and 48 healthy controls(HC) by enzyme-linked immunosorbent assay(ELISA).The relationships between serum Sema 5A and disease activity, radiographic severity and laboratory parameters were investigated in RA patients.(2)RAW264.7 cells were treated with different concentrations of Sema 5A(0,0.5,1,2.5,5 µg/ml).After 7 days, tartrate-resistant acid phosphate(TRAP) staining was performed. The mRNA levels of TRAP, cathepsin-K and matrix metallopeptidase 9(MMP-9) were tested using real-time polymerase chain reaction (RT-PCR).(3)Bone resorption area of dentine slides cultured with RAW264.7 cells was calculated after Sema 5A(5µg/ml) treatment. Results: (1)The serum Sema 5A in RA patients[(5.24±0.59)µg/L] was significantly higher than those in healthy controls[(2.93±0.34)µg/L,P<0.01] and OA patients[(2.68±0.47)µg/L,P<0.05]. The Sema 5A level in RA patients was positively correlated with disease activity score with 28 joint using C-reactive protein(DAS28-CRP), clinical disease activity index (CDAI),C-reactive protein(CRP) and sharp scores(P<0.05 or P<0.01).In addition,the serum Sema 5A in RA patients with positive anti-cyclic citrullinated peptide(CCP) antibody was significantly greater than that of anti-CCP antibody-negative patients(P<0.05).(2)After RAW264.7 cells were treated with Sema 5A, the number of TRAP positive osteoclasts increased according to the increase of Sema 5A concentration with maximal effect at 5 µg/ml. Meanwhile, Sema 5A promoted mRNA expression of TRAP,Cathepsin-K and MMP-9.(3)Bone resorption area increased when RAW264.7 cells were treated with Sema 5A(5 µg/ml). Conclusions: Serum Sema 5A is elevated in RA patients and correlated with disease activity and radiographic severity. Sema 5A promotes osteoclastogenesis of RAW264.7 cells.
Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Autoanticorpos/sangue , Osteoartrite/imunologia , Osteogênese/fisiologia , Semaforinas/sangue , Artrite Reumatoide/sangue , Proteína C-Reativa/imunologia , Proteína C-Reativa/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Osteoartrite/sangue , Osteoartrite/patologia , Osteogênese/imunologiaRESUMO
To investigate the relationship between plasma soluble semaphorin4D (sSema4D) and obstructive sleep apnea-hypopnea syndrome (OSAHS), and to ascertain the effect of sSema4D on cognitive dysfunction in patients with OSAHS. We prospectively recruited 30 men with moderate-severe OSAHS diagnosed by polysomnography, and 30 healthy controls with matched gender, age and education level. Montreal Cognitive Assessment (MoCA) was administered to determine cognitive impairment. Plasma sSema4D levels were measured. Among the total of 60 study patients, the overall plasma sSema4D level was 7.81 ± 1.91 ng/ml. Plasma sSema4D level in OSAHS group was significantly higher than that in controls (8.92 ± 1.79 vs 6.70 ± 1.28 ng/ml, p < 0.001). In OSAHS subgroup, patients with cognition impairment (CI) had higher plasma sSema4D level (10.50 ± 1.16 vs 8.00 ± 1.41 ng/ml, p < 0.001) and apnea-hypopnea index (AHI) (48.1 ± 14.0 vs 30.3 ± 9.2, p < 0.001) than those in non-CI group. Multiple logistic regression revealed that plasma sSema4D level (AOR 2.824, 95 % CI 1.562-5.103; p = 0.001) and BMI (AOR 2.237, 95 % CI 1.345-3.722; p = 0.002) were significantly associated with OSAHS, and plasma sSema4D was a significant predictor of CI after adjustment for other confounders (AOR 4.956, 95 % CI 1.581-15.538; p = 0.006). OSAHS patients, especially those with cognition impairment, are featured by elevated plasma sSema4D level, and sSema4D is significantly associated with cognition impairment induced by OSAHS.
Assuntos
Antígenos CD/sangue , Disfunção Cognitiva , Semaforinas/sangue , Apneia Obstrutiva do Sono , Adulto , China , Disfunção Cognitiva/sangue , Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico , Feminino , Humanos , Testes de Inteligência , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Estudos Prospectivos , Reprodutibilidade dos Testes , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Estatística como AssuntoRESUMO
Novel targets for action of the class IV semaphorin Seam4D have been identified in the immune system. The low-affinity CD72 receptor for Seam4D was detected not only on B lymphocytes, but also in a proportion of T cells, whereas the high-affinity semaphorin receptor, plexin B1, originally considered to belong to non-immune cells, proved to be in a great proportion of intact T and B cells. Seam4D is constitutively expressed in B cells, which, along with T cells, can serve as a source of both membrane and soluble semaphorin. The results obtained make significant adjustments in understanding of Seam4D effects in lymphoid cells.
Assuntos
Antígenos CD/sangue , Sistema Imunitário , Ativação Linfocitária/imunologia , Proteínas do Tecido Nervoso/sangue , Receptores de Superfície Celular/sangue , Semaforinas/sangue , 5'-Nucleotidase/sangue , 5'-Nucleotidase/imunologia , Antígenos CD/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Humanos , Linfócitos/imunologia , Linfócitos/metabolismo , Proteínas do Tecido Nervoso/imunologia , Receptores de Superfície Celular/imunologia , Semaforinas/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
INTRODUCTION: B cell receptor (BCR) -mediated signals are enhanced when CD72 expression is deficient on B cells in autoimmune diseases. The significance of soluble CD72 (sCD72) has not been elucidated. METHODS: Soluble CD72 was analyzed in the serum of 159 SLE patients, 40 rheumatoid arthritis (RA) patients, and 100 healthy individuals. Correlations between sCD72 and SLE disease activity (SLEDAI) were assessed. RESULTS: Soluble CD72 was found increased in SLE patients, when compared to both RA patients and healthy individuals (20.2 ± 1.2 ng/ml; 10.6 ± 4.6 ng/ml and 7.2 ± 3.3 ng/ml; p < 0.001). Soluble CD72 level was significantly higher in SLE patients with renal involvement than in patients without (31.8 ± 2.3 ng/ml vs 13.9 ± 0.9 ng/ml; p < 0.001) and also with the presence of auto-antibodies. CONCLUSION: Soluble CD72 is significantly increased in SLE patients mainly in those with renal involvement. Increased sCD72 may become a potential biomarker for renal involvement in SLE.
Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação de Linfócitos B/sangue , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Anticorpos Antinucleares/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Linfócitos B/imunologia , Biomarcadores/sangue , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Semaforinas/sangue , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to evaluate the serum soluble semaphorin 4D (sSema4D) in patients with atrial fibrillation and to investigate the relationship of serum sSema4D with left atrial diameter (LAD). MATERIAL AND METHODS: We studied a total of 113 patients who were subdivided into paroxysmal and non-paroxysmal (included persistent and permanent) atrial fibrillation groups, respectively. Another 55 subjects without atrial fibrillation were enrolled as the healthy control group. Serum levels of soluble semaphorin 4D (Sema4D) were measured in all subjects using the enzyme-labeled immunosorbent assay method. We also evaluated the coagulation parameters and left atrial diameters. RESULTS: Patients with paroxysmal and non-paroxysmal atrial fibrillation had significantly higher sSema4D level compared with controls (8.50±2.19 ng/mL and 9.30±2.28 ng/mL vs. 6.56±1.27 ng/ml, P<0.05). Serum sSema4D concentrations were elevated in patients with non-paroxysmal atrial fibrillation compared to those with paroxysmal atrial fibrillation (P<0.001). The level of sSema4D was positively correlated with LAD (r=0.606, P<0.001). Multivariate logistic regression analysis revealed that serum sSema4D, LAD, male sex, heart rate, hypertension, and coronary artery disease were associated with atrial fibrillation (P<0.05). CONCLUSIONS: Serum sSema4D levels are increased in patients with atrial fibrillation and are independently associated with atrial remodeling.
Assuntos
Antígenos CD/sangue , Fibrilação Atrial/sangue , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/fisiologia , Átrios do Coração/anatomia & histologia , Semaforinas/sangue , Idoso , Coagulação Sanguínea , Ecocardiografia , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação da Expressão Gênica , Frequência Cardíaca , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Estudos RetrospectivosRESUMO
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the CNS and a leading cause of lasting neurologic disabilities in young adults. Although the precise mechanism remains incompletely understood, Ag presentation and subsequent myelin-reactive CD4(+) T cell activation/differentiation are essential for the pathogenesis of MS. Although semaphorins were initially identified as axon guidance cues during neural development, several semaphorins are crucially involved in various phases of immune responses. Sema4A is one of the membrane-type class IV semaphorins, which we originally identified from the cDNA library of dendritic cell (DC). Sema4A plays critical roles in T cell activation and Th1 differentiation during the course of experimental autoimmune encephalomyelitis, an animal model of MS; however, its pathological involvement in human MS has not been determined. In this study, we report that Sema4A is increased in the sera of patients with MS. The expression of Sema4A is increased on DCs in MS patients and shed from these cells in a metalloproteinase-dependent manner. DC-derived Sema4A is not only critical for Th1 but also for Th17 cell differentiation, and MS patients with high Sema4A levels exhibit Th17 skewing. Furthermore, patients with high Sema4A levels have more severe disabilities and are unresponsive to IFN-ß treatment. Taken together, our results suggest that Sema4A is involved in the pathogenesis of MS by promoting Th17 skewing.
Assuntos
Diferenciação Celular/imunologia , Interferon beta/uso terapêutico , Esclerose Múltipla/imunologia , Esclerose Múltipla/terapia , Semaforinas/biossíntese , Células Th17/imunologia , Regulação para Cima/imunologia , Sequência de Aminoácidos , Animais , Diferenciação Celular/genética , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Esclerose Múltipla/patologia , Ratos , Semaforinas/sangue , Semaforinas/deficiência , Semaforinas/metabolismo , Células Th17/metabolismo , Células Th17/patologia , Regulação para Cima/genéticaRESUMO
The JMH blood group system consists of six high-prevalence antigens. These antigens are located on the Sema7A protein. The molecular basis of the JMH1- phenotype is not known; however, single nucleotide changes in the SEMA7A gene on chromosome 15 account for the other JMH antigens. JMH1, commonly known as JMH, is most notable because transient depression of the antigen occurs and anti-JMH may develop. These antibodies are most commonly observed and are not significant in transfusion. Antibodies developed in the rare JMH variant types may cause reduced red cell survival. This review provides a general overview of the JMH blood group system, including the serologic and molecular characteristics as well as proposed functions of the Sema7A protein.