Summary
Objectives. To explore the possible involvement of the proinflammatory and prothrombotic cytokine TNFα in APS by determining the plasma levels in patients and to test for association of TNFA promoter polymorphisms and HLA class II genotypes with both plasma TNF and disease. Patients and Method. We studied 83 Caucasoid patients with APS and two groups of healthy controls. TNFα levels were determined in plasma from 35 patients’ and 21 controls using a highly sensitive sandwich ELISA. The full patient group was genotyped together with 95 ethnically matched healthy controls. -308 and -238 TNFA promoter polymorphisms were assessed by ARMS-PCR. HLA-DQB1, DQA1 and DRB1 genotypes were determined by PCR using sequence specific primers. Results. TNFα levels were significantly higher in patients with APS than healthy controls (median 2.95 pg/ml [range 0.51-10.75] vs. 0.95 pg/ml [0.51-1.6], respectively; p = 0.0001). Frequencies of TNFA-308*2 genotype did not differ between patients and controls. In contrast, TNFA-238*A positive genotype was more frequent in APS patients with arterial thrombosis and pregnancy loss than in controls (OR 3.7 [95% CI 1.37-10.1], p = 0.007 and OR 3.95 [95% CI 1.3-11.7], p = 0.01; respectively). DQB1*0303-DRB1*0701 haplotype was associated with TNFA-238*A in the control group (OR 96.0 [95% CI 9.6-959], p 0.0001) as well as in APS patient’s group (OR 54.2 [95% CI 9.6-306.5], p 0.0001). Conclusions. Raised plasma TNFα levels were found in patients with APS. As a prothrombotic and proinflammatory cytokine, TNFα may be involved in the development of clinical features of APS. The lack of correlation between the TNFA-238 polymorphism and plasma levels associated with disease suggests that the TNFα genetic marker may only indirectly relate to protein levels by virtue of allelic association with a functional marker which may reside in the HLA class II region.
CD8ab heterodimers are mainly expressed on cytotoxic T lymphocytes. This study demonstrated the detection of CD8ab heterodimers on human monocytes by whole blood erythrocyte lysis method in flow cytometry. Results revealed that CD8ab heterodimers were not produced by monocytes themselves, but were transferred from T cells to monocytes when these cells were coincubated in plasma and with anti-CD8 monoclonal antibody (mAb). For completion of CD8 translocation from T cells to monocytes, cellto-cell contact between T cells and monocytes, as well as binding of the Fc portion of the anti-CD8 mAb and Fcc receptor II (FccRII) on monocytes were required. Furthermore, the dynamism of cell membrane and cytoskeleton were involved in the mechanism of CD8 translocation. Interestingly, CD3 and abT cell receptor (TCR) were also transferred from T cells to monocytes accompanied by CD8. These phenomena are consistent with Ab-dependent and FccR-mediated trogocytosis, which is recently recognized as one of the intercellular communication processes of the immune system. Trogocytosis means exchange of plasma membrane including cell surface molecules in conjugates formed between immune cells. Results of this study could provide another model of trogocytosis and clearly indicated that putative plasma factors were critically implicated in the mechanism of Ab-dependent and FccR-mediated trogocytosis. ' 2010 International Society for Advancement of Cytometry
In an attempt to clarify the biological nature of a human endogenous retrovirus (HERV), HERV-R, which is a single-copy type of HERVs and is conserved as a full-length viral sequence, the expression of HERV-R mRNA in normal autopsied systemic organs was examined by Northern blot analysis. The expression showed different levels among individuals, with the adrenal glands expressing the highest level of HERV-R among all organs tested, except for the placenta. In various adrenal tumors, HERV-R was expressed at high levels in all cortical adenomas but less so in pheochromocytomas. In situ hybridization revealed the expression of HERV-R to be localized in all layers of the adrenal cortex, but not in the medulla. This high-level expression of HERV-R in the adrenal cortex may possibly relate to differentiation and/or steroid production by adrenocortical cells.
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