1,720,992 research outputs found
The clearance of apoptotic cells: Implications for autoimmunity
Full text linkApoptosis has been clearly characterised by the ability to limit the activation of inflammatory responses through the disposal of the apoptotic cell by rapid uptake by phagocytes. The exposure of phosphatidylserine deriving from the loss of plasma lipid asymmetry is the early membrane signal which alerts the phagocyte about the imminent apoptotic death of the cell. Also modifications of membrane carbohydrate groups on apoptotic cells contribute to phagocyte recognition. Soluble proteins such as C1q, mannose-binding lectin, surfactant proteins A and D, C-reactive protein, C3bi, β2-glycoprotein I and growth arrest specific gene-6 bind to apoptotic cells and act as 'opsonins' thus favouring their clearance. A redundant and promiscuous system of receptors including integrins, scavenger receptors, CR3 and CR4, calreticulin, CD14 and Mer receptor ensures an efficient and rapid uptake of apoptotic cells. In animal models and in human pathology, single genetic defects of molecules involved in apoptotic cell clearance seem to be the main determinant in the development of autoimmunity. The uptake of apoptotic cells by phagocytes provides an immunomodulatory effect in that it triggers the release of anti-inflammatory cytokines, inhibits the production of inflammatory cytokines and leads to T cell tolerance. Impaired clearance of apoptotic cells or the presence of 'danger' signals may modify the balance between tolerance induction and activation of T cells leading to an effective autoimmune response. © 2002 Elsevier Science B.V. All rights reserved
Treatment of thrombosis associated with immunological risk factors
No full textThe clinical management of the antiphospholipid syndrome is aimed at assessing the thrombotic risk of an individual in order to undertake primary prevention for the asymptomatic subject positive for antiphospholipid antibodies or prophylaxis of major ischaemic events for the patient who has already experienced thrombosis. Lack of immunological parameters with a clear predictive value and the current concept that thrombosis is a multifactorial disease suggest that all the known acquired and genetic thrombotic risk factors should be taken into account in antiphospholipid syndrome. Low-dose aspirin and hydroxychloroquine have been proven useful in primary prevention. While convincing evidence has been provided that aspirin and hydroxy chloroquine do not prevent secondary thrombosis, much debate has recently developed on the level of oral anticoagulation needed to guarantee this prevention. Main concerns are also related to duration of anticoagulation therapy, risk of bleeding, and the increased risk of thrombosis as a result of withdrawal of the anticoagulant. Lowmolecular-weight heparin has recently emerged as a valid and safe alternative for those conditions that require transient interruption or withdrawal of anticoagulation. Although treatment of the catastrophic antiphospholipid syndrome is largely empirical, the therapeutic approach based on plasmapheresis associated with immunosupression or intravenous immunoglobulin seems to be the most promising. Most attention has recently been paid to the role of oxidative stress in the pathogenesis of antiphospholipid syndrome, as a correlation between lipid peroxidation and antiphospholipid antibodies has been demonstrated. Our studies showed that lipid peroxidation may contribute to the activation of the clotting system observed in antiphospholipid syndrome and that markers of both procoagulant state and increased lipid peroxidation can be modified by experimental antioxidant treatment
Relapsing polychondritis: A syndrome rather than a distinct clinical entity?
No full text[No abstract available
Anti-tumour necrosis factor (TNF) alpha treatment of rheumatoid arthritis (infliximab) selectively down regulates the production of interleukin (IL) 18 but not of IL12 and IL13
No full textObjective: To measure interleukin (IL) 18 serum concentrations in patients with rheumatoid arthritis (RA) undergoing infliximab treatment (tumour necrosis factor (TNF) alpha blockade) and to evaluate the concomitant modification of IL12 and IL13 serum concentrations, two cytokines belonging to the Th1 and Th2 profile respectively and biologically related to IL18. Methods: Ten patients with RA not responding to disease modifying antirheumatic drugs (DMARDs) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks. Serum samples were collected from all patients before each infusion and assayed for IL18, IL12, and IL13 by enzyme linked immunosorbent assay (ELISA); IL18 was also measured eight weeks after the, last infusion. Results: Serum concentrations of IL18 in all patients were already markedly reduced from baseline after two weeks (p<0.005). Serum IL18 was also decreased in a stable manner after six (p<0.01) and 14 weeks (p<0.01) compared with baseline concentrations. No significant modifications were found in serum concentrations of IL12 and IL13 at any time point.. Conclusion: There was a rapid and persistent decrease in serum concentrations of IL18 in all the patients studied. This result provides evidence of an in vivo regulation of IL18 by TNFα and suggests that anti-TNFα therapy is likely to interrupt the synergistic effect between these two cytokines
Polymorphism of the Duffy erythrocyte chemokine receptor in Italian patients with Behcet's disease
No full textThis study examined the hypothesis that the polymorphism of Duffy antigen receptor for chemokines (DARC) predisposes to and/or influences the clinical manifestations of Behçet's disease. The serum levels of IL-8 and monocyte chemotactic peptide (MCP)-1, two DARC-binding chemokines, were investigated and related to this polymorphism. Twenty-eight patients with Behçet's disease and 30 healthy blood donors were included in the study. No null phenotypes were found among the patients studied, and the frequencies of the other phenotypes (Fy(a+b-), Fy(a+b+), and Fy(a-b+)) did not significantly differ from those found in the blood donor group or reported in the general Caucasian population. No difference was found between the single phenotypes in terms of IL-8 and MCP-1 serum levels, and no relevant association between the clinical characteristics, Behçet's disease-associated human leukocyte antigen (HLA)-B51, and single phenotypes was observed. This investigation indicates that DARC is not a genetic trait significantly associated with or predisposing to Behçet's disease, at least in Caucasian Italians. However, the role of this polymorphism in the development and in the clinical course of the disease awaits further investigation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Anti-cardiolipin antibodies in HIV infection are true antiphospholipids not associated with antiphospholipid syndrome
No full textThe aim of the present study was to evaluate the fine specificity of anticardiolipin (aCL) antibodies detectable in the sera of patients with HIV infection. aCL are generally associated with thrombotic events in autoimmune diseases. A solid phase ELISA which discriminates between aCL binding to phospholipids and aCL binding to phospholipid/β2-glycoprotein I (cofactor) complex was employed. Thirty-nine HIV and 20 aCL positive systemic lupus erythematosus (SLE) sera were examined. In HIV sera, reduced binding to phospholipid was seen if cofactor was added. On the contrary, in SLE-sera the cofactor improved aCL binding. No thrombotic events were recorded in HIV infected subjects presenting with aCL. Thus, aCL in HIV infection and in SLE appear to have different specificities. In HIV infection the true epitope of aCL is likely to be on the phospholipid component only, whereas in SLE aCL seem directed against the cofactor/CL complex. Considering the anticoagulant role of β2-glycoprotein I, this observation might account for the lack of thrombosis in HIV patients with 'true' aCL
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