Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet activation has been suggested to play a crucial role in the pathogenesis of haemostatic disorders in antiphospholipid syndrome (APS). In 16 patients with primary APS (PAPS) we investigated by flow cytometry the presence of circulating activated platelets as defined by the surface expression of activation-dependent glycoproteins CD62 and CD63. In addition, the relationships among activated platelets, thrombocytopenia, antiphospholipid antibodies (aPL) and platelet associated IgG (PalgG) were evaluated. Compared to normal subjects CD62, but not CD63 expression, was found significantly increased in patients. All thrombocytopenic subjects showed a percentage of CD62 expressing platelets above the cut off. In thrombocytopenics a significantly increased percentage of CD62 and higher levels of aCL IgG were found compared to PAPS patients with normal platelet count. No correlation was found between activated platelets and both lupus anticoagulant antibodies and PalgG. Our data demonstrate that circulating activated platelets are detectable by flow cytometry in the majority of PAPS patients and suggest the existence of a relationship among activated platelets, thrombocytopenia and aPL levels.
Lupus 1997
PMID:Flow cytometric detection of circulating activated platelets in primary antiphospholipid syndrome. Correlation with thrombocytopenia and anticardiolipin antibodies. 910 34

Thromboembolism is a common occurrence in patients with the antiphospholipid syndrome (APS). The mechanism responsible for this phenomenon is unclear; there are several theories. One possibility is that a pathogenic interaction exists between antiphospholipid antibodies and platelets, leading to their activation. This study examined the expression of the platelet activation markers CD62 and CD63 by flow cytometry in 20 patients with the primary antiphospholipid syndrome (PAPS). Levels of soluble P-selectin were also assayed. Reticulated platelets were measured as an indicator of increased platelet production and/or turnover. Median CD63 expression was significantly increased in patients (14.3%) compared to a group of healthy controls (10.1%, P = 0.0008). There was no significant difference in median CD62 expression or percent reticulated platelets between the two groups. The median level of soluble P-selectin was significantly higher in PAPS patients (35.5 ng/ml) compared to controls (18.8 ng/ml, P = 0.0028). Patients receiving aspirin had lower median CD63 values (13.1%) when compared to those patients who were not (18.0%, P = 0.023). However, aspirin therapy did not prevent significant platelet activation occurring in some individual patients. Our data suggest that although not excessive, there is a degree of increased platelet activation in some PAPS patients, which is not always suppressed by antiplatelet therapy with aspirin.
Lupus 1998
PMID:Platelet activation and turnover in the primary antiphospholipid syndrome. 969 37

Platelets play an important part in normal haemostasis, and are likely to be involved in the thromboembolism seen in the primary antiphospholipid syndrome (PAPS). Evidence exists for platelet activation in this disorder, and new flow cytometric techniques have made it possible to detect low levels of activation. We have previously studied the expression of the platelet activation markers CD62p and CD63, percentage of reticulated platelets, and levels of soluble P-selectin in a group of PAPS patients. Median platelet CD63 expression and plasma soluble P-selectin levels were significantly increased in PAPS patients compared to a group of controls; there was no difference in reticulated platelet percentages between the two groups. Additional assays of platelet activation (PAC-1 expression, Annexin V binding, platelet microparticles and complexes) are being developed and assessed with respect to disease activity, thrombosis risk and effects of antithrombotic therapy.
Lupus 1998
PMID:Platelet activation markers and the primary antiphospholipid syndrome (PAPS). 981 73

It is possible that platelet activation may play a pathogenic role in the increased risk of thrombosis associated with antiphospholipid antibodies (APA). In this study, levels of in vivo platelet activation were measured in 20 patients with primary antiphospholipid syndrome (PAPS) and 30 systemic lupus erythematosus (SLE) patients (14 of whom had secondary APS) using sensitive flow cytometry. Soluble P-selectin levels were also assayed. Platelet CD63 expression was significantly higher in PAPS than normal controls (P = 0.007), as well as SLE patients with and without secondary APS (P = 0.03 and P = 0.002 respectively). PAC-1 binding was significantly higher in PAPS than the control group (P = 0.007) and SLE patients without APS (P = 0.015). Platelet-leucocyte complexes were significantly higher in SLE patients than both PAPS and the control group, and platelet-monocyte complexes were significantly increased in PAPS compared with the control group. (Platelet-leucocyte complexes were also significantly higher than controls in 10 rheumatoid arthritis (RA) patients without APA). Soluble P-selectin levels were significantly higher in PAPS and SLE patients than the control group. Platelet CD62p expression, annexin V binding and platelet microparticle numbers were not increased in PAPS or SLE patients. We conclude that there is evidence of increased platelet activation in PAPS and SLE, and this is important to note as it may have potential therapeutic implications with respect to use of antiplatelet agents in these patients.
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PMID:Increased circulating platelet-leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis. 1170 49

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by defective immune tolerance combined with immune cell hyperactivity resulting in the production of pathogenic autoantibodies. Previous gene expression studies employing whole blood or peripheral blood mononuclear cells (PBMC) have demonstrated that a majority of patients with active disease have increased expression of type I interferon (IFN) inducible transcripts known as the IFN signature. The goal of the current study was to assess the gene expression profiles of isolated leukocyte subsets obtained from SLE patients. Subsets including CD19(+) B lymphocytes, CD3(+)CD4(+) T lymphocytes and CD33(+) myeloid cells were simultaneously sorted from PBMC. The SLE transcriptomes were assessed for differentially expressed genes as compared to healthy controls. SLE CD33(+) myeloid cells exhibited the greatest number of differentially expressed genes at 208 transcripts, SLE B cells expressed 174 transcripts and SLE CD3(+)CD4(+) T cells expressed 92 transcripts. Only 4.4% (21) of the 474 total transcripts, many associated with the IFN signature, were shared by all three subsets. Transcriptional profiles translated into increased protein expression for CD38, CD63, CD107a and CD169. Moreover, these studies demonstrated that both SLE lymphoid and myeloid subsets expressed elevated transcripts for cytosolic RNA and DNA sensors and downstream effectors mediating IFN and cytokine production. Prolonged upregulation of nucleic acid sensing pathways could modulate immune effector functions and initiate or contribute to the systemic inflammation observed in SLE.
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PMID:SLE peripheral blood B cell, T cell and myeloid cell transcriptomes display unique profiles and each subset contributes to the interferon signature. 2382 84

Aberrant expression of CXCR4 has been indicated to play a role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanism of CXCR4 dysregulation in SLE is unclear. This study is aimed to explore the clinical significance and possible mechanisms of abnormal CXCR4 expression on B cells from patients with untreated SLE. Expression of CXCR4 on peripheral B cells was determined by flow cytometry and western blotting. Freshly isolated B cells were cultured with exogenous interleukin 21(IL-21) in the presence or absence of CD40 ligand (CD40L) plus anti-IgM antibody (aIgM), and changes in CXCR4 expression were detected. Involvement of phosphatidylinositol 3 kinase (PI3K)/Akt and Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathways was assessed by adding blocking agents Ly294002 and AG490. Since CD63 is reported to mediate endosomal recruitment of CXCR4 and BCL6 is capable of silencing CD63 gene transcription, we also measured BCL6 and CD63 gene transcription with real-time PCR. It was shown that CXCR4 expression on B cells was significantly upregulated in SLE patients, especially in those with lupus nephritis, and was positively correlated with SLE Disease Activity Index scores and negatively with the serum complement 3 levels (P<0.05). Downregulation of CXCR4 by IL-21 was intact. In contrast, a similar effect of aIgM plus CD40L in downregulating CXCR4 expression was defective in SLE patients but was restored by co-stimulation with IL-21 in vitro. Both Ly294002 and AG490 promoted downregulation of surface CXCR4 expression on B cells from SLE patients (P=0.078 and P=0.064). Furthermore, B cells from SLE patients exhibited diminished CD63 mRNA and enhanced BCL6 mRNA expression (both P<0.05). To sum up, CXCR4 was overexpressed on SLE B cells, positively correlating with disease activity and kidney involvement. Overactivation of the PI3K/Akt and JAK/STAT pathways as well as defective CD63 synthesis may contribute to CXCR4 dysregulation in SLE.
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PMID:Contribution and underlying mechanisms of CXCR4 overexpression in patients with systemic lupus erythematosus. 2766 47