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1.
Int Immunopharmacol ; 140: 112743, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39094356

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by immune mechanisms dysregulation, leading to the production of diverse autoantibodies. However, the immune pathways underlying B-cell function and phenotypic abnormalities related to SLE pathogenesis remain incompletely understood. OBJECTIVE: To explore new markers of SLE activity and potential targets for SLE immunotherapy. METHODS: Collect peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls (HC). Use flow cytometry to detect CD39 and CD73 expression on B cell subsets and enzyme-linked immunosorbent assay (ELISA) to measure adenosine (ADO) concentrations in SLE patients' serum. Compare CD39+CD73+ B cell subsets frequency and ADO concentrations in SLE patients and HC group. Additionally, analyze the correlation between CD39+CD73+ B cell subsets frequency and clinical laboratory parameters. RESULTS: CD39 and CD73 are simultaneously highly expressed on CD19+ B cell subsets, with significantly lower frequency of CD39+CD73+ B cell subsets in SLE patients compared to HC group. This frequency negatively correlates with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), C-reactive protein (CRP), and anti-double-stranded DNA (anti-dsDNA) antibodies, while positively correlating with IgM and prothrombin time (PT). Additionally, the frequency of CD39+CD73+ B cell subsets is significantly negatively correlated with IL-6 and IFN-α. In vitro cell experiments demonstrate that adenosine significantly inhibits R848-induced inflammatory cytokine production in a dose-dependent manner. CONCLUSION: The frequency of CD39+CD73+ B cell subsets of SLE patients is decreased, correlating with clinical laboratory parameters and disease activity. Simultaneously, ADO concentration in the patients' serum is reduced. The CD39+CD73+ B cell/ADO pathway may represent a novel immunotherapy strategy for SLE.


Assuntos
5'-Nucleotidase , Adenosina , Apirase , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/sangue , Apirase/metabolismo , Apirase/imunologia , 5'-Nucleotidase/imunologia , 5'-Nucleotidase/metabolismo , Feminino , Masculino , Adulto , Adenosina/metabolismo , Adenosina/imunologia , Subpopulações de Linfócitos B/imunologia , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Pessoa de Meia-Idade , Antígenos CD/metabolismo , Antígenos CD/imunologia , Adulto Jovem , Índice de Gravidade de Doença
2.
Immunol Lett ; 258: 1-7, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37127120

RESUMO

BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease primarily affecting the exocrine glands, which has a variety of clinical manifestations and unclear pathogenic mechanisms. Adenosine deaminase (ADA) is an enzyme involved in the breakdown of purines, and changes in its activity have been associated with a number of autoimmune diseases. This study aims to investigate the relationship between serum ADA activity and disease activity in patients with pSS. METHODS: In this study, 196 patients with pSS and 196 healthy controls were enrolled. Serum ADA activity and clinical laboratory parameters were collected and analyzed in both groups. Pearson correlation analysis was used to examine the correlation between ADA activity and clinical laboratory parameters, as well as the correlation between ADA activity and the disease activity score. RESULTS: Compared with healthy controls, the activity of ADA in the serum of pSS patients was significantly increased (P < 0.0001), and the ADA activity was significantly decreased after immunosuppressive treatment (P < 0.0001). Correlation analysis revealed that the activity of ADA was significantly positively correlated with erythrocyte sedimentation rate (ESR) (r = 0.3, P < 0.0001) and serum immunoglobulin G (IgG) levels (r = 0.5, P < 0.0001), and significantly negatively correlated with high-density lipoprotein (HDL) (r = -0.4, P < 0.0001). Furthermore, there was a significant positive correlation between ADA activity and the disease activity score as measured by the Sjögren's Syndrome Disease Activity Index (SSDAI) (r = 0.4, P < 0.0001). CONCLUSION: This study found that patients with pSS have higher activity of ADA in serum, which is associated with disease activity as measured by SSDAI. These results suggest that ADA activity may be a potential biomarker for evaluating disease activity and treatment efficacy in pSS patients. Additionally, ADA may be a potential target for the treatment of pSS patients.


Assuntos
Doenças Autoimunes , Síndrome de Sjogren , Humanos , Adenosina Desaminase , Biomarcadores , Síndrome de Sjogren/diagnóstico , Resultado do Tratamento
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