1,721,191 research outputs found
pitfalls of antinuclear antibody detection in systemic lupus erythematosus: the positive experience of a national multicentre study
No full textThe two hit hypothesis in the antiphospholipid syndrome: acute ischaemic heart involvement after valvular replacement despite anticoagulation in a patient with secondary APS
No full textTumour Necrosis Factor α Antagonists in the Treatment of Rheumatoid Arthritis: An Immunological Perspective.
No full textRheumatoid arthritis (RA) is one of the most prevalent autoimmune conditions, affecting approximately 1 % of the adult population. It is associated with decreased quality of life and considerable morbidity and mortality. Various inflammatory cells, including macrophages, neutrophils, mast cells, natural killer cells, B and T cells and stromal cells play key pathophysiological roles in joint inflammation and RA progression. Several cytokines, including interleukin (IL)-1α and/or IL-1β, and tumour necrosis factor (TNF)-α, are involved at each stage of RA pathogenesis; namely, by augmenting autoimmunity, sustaining long-term inflammatory synovitis and promoting joint damage. Different cell types are involved in RA pathogenesis through upregulation of several cytokine and soluble pro-inflammatory mediators. As early as the late 1980s, TNF had been identified as a potential target in RA. Five anti-TNF drugs, infliximab, adalimumab, certolizumab pegol, etanercept and golimumab, are now approved for the treatment of RA in various countries. All are bivalent monoclonal antibodies, with the exception of the monovalent certolizumab and etanercept, which is an engineered dimeric receptor. Although all react with and neutralise soluble TNF in vitro, structural differences in the molecules may contribute to differences in their therapeutic effects and the occurrence of side effects. Pegylated certolizumab permits once-monthly dosing. Other mechanisms of action proposed to be important for the efficacy of anti-TNF agents are as follows: induction of apoptosis of both monocytes and T cells; neutralization of membrane TNF; antibody-dependent cell-mediated and complement-dependent cytotoxicity; and reverse signaling via membrane TNF
Humoral autoimmunity against vascular epithelia: theory or reality?
No full textDespite the discovery of anti-endothelial cell antibodies
(AECA) in a heterogeneous group of disorders characterized
by endothelial damage, their pathogenic role is
still debated. Experimental in vitro models indicate that
they can either damage endothelial cells or trigger cell
signaling by reacting with as yet undefined surface
molecules. However, clinical studies suggest that, in
addition to AECA, other pathogenic mechanisms are
involved in the vasculitic process. Recently, antibodies
specific for b2 glycoprotein I, the phospholipid-binding
protein targeted by anti-phospholipid antibodies, have
been shown to display anti-endothelial activity. These
autoantibodies recognize b2 glycoprotein I adhered to
the endothelium and induce a cell perturbation that
might underlie the thrombophilic state of the antiphospholipid
syndrome
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