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Autoimmune Rheumatic Diseases (autoimmune + rheumatic_disease)

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Medical Sciences100%

Selected Abstracts

Abnormal CTLA-4 function in T cells from patients with systemic lupus erythematosus

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2010
Elizabeth C. Jury
Abstract CTLA-4 is a critical gatekeeper of T-cell activation and immunological tolerance and has been implicated in patients with a variety of autoimmune diseases through genetic association. Since T cells from patients with the autoimmune disease systemic lupus erythematosus (SLE) display a characteristic hyperactive phenotype, we investigated the function of CTLA-4 in SLE. Our results reveal increased CTLA-4 expression in FOXP3, responder T cells from patients with SLE compared with other autoimmune rheumatic diseases and healthy controls. However, CTLA-4 was unable to regulate T-cell proliferation, lipid microdomain formation and phosphorylation of TCR-, following CD3/CD28 co-stimulation, in contrast to healthy T cells. Although lupus T cells responded in vitro to CD3/CD28 co-stimulation, there was no parallel increase in CTLA-4 expression, which would normally provide a break on T-cell proliferation. These defects were associated with exclusion of CTLA-4 from lipid microdomains providing an anatomical basis for its loss of function. Collectively our data identify CTLA-4 dysfunction as a potential cause for abnormal T-cell activation in patients with SLE, which could be targeted for therapy. [source]

Report on the Second Asia Autoimmunity Forum, Hong Kong, 3,5 March 2006

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2006
S. KAVIKONDALA
Abstract The Second Asia Autoimmunity Forum was jointly organized by the Hong Kong Society of Rheumatology, the University of Hong Kong, and the Singapore National Arthritis Foundation, and was attended by over 200 delegates from around Asia. More than 20 invited international and regional experts in the field of autoimmune rheumatic diseases from China, Greece, Hong Kong, Israel, Italy, the Netherlands, Singapore, and South Korea attended the meeting. A total of eight plenary lectures and four clinical symposia covered topics ranging from the role of dendritic cells and various genes in the pathogenesis of systemic lupus erythematosus, the changes in disease manifestations during pregnancy in lupus, advances on genetic studies in ankylosing spondylitis (AS), the role of dendritic cells and cytokines in the pathogenesis of rheumatoid arthritis (RA) to the novel emerging targets for treatment of RA, systemic sclerosis (SSc) and primary Sjogren's syndrome (pSS). It was an excellent avenue promoting the co-ordination and exchange of knowledge in the area of autoimmune rheumatic diseases in Asia. [source]

Autoantigens in systemic autoimmunity: critical partner in pathogenesis

JOURNAL OF INTERNAL MEDICINE, Issue 6 2009
A. Rosen
Abstract. Understanding the mechanisms of human autoimmune rheumatic diseases presents a major challenge, due to marked complexity involving multiple domains, including genetics, environment and kinetics. In spite of this, the immune response in each of these diseases is largely specific, with distinct autoantibodies associated with different disease phenotypes. Defining the basis of such specificity will provide important insights into disease mechanism. Accumulating data suggest an interesting paradigm for antigen selection in autoimmunity, in which target tissue and immune effector pathways form a mutually reinforcing partnership. In this model, distinct autoantibody patterns in autoimmunity may be viewed as the integrated, amplified output of several interacting systems, including: (i) the specific target tissue, (ii) the immune effector pathways that modify antigen structure and cause tissue damage and dysfunction, and (iii) the homeostatic pathways activated in response to damage (e.g. regeneration/differentiation/cytokine effects). As unique antigen expression and structure may occur exclusively under these amplifying circumstances, it is useful to view the molecules targeted as ,neo-antigens', that is, antigens expressed under specific conditions, rather than ubiquitously. This model adds an important new dynamic element to selection of antigen targets in autoimmunity, and suggests that the amplifying loop will only be identified by studying the diseased target tissue in vivo. [source]

Anti-endothelial cell antibodies in rheumatic heart disease

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2010
V. Scalzi
Summary To evaluate the anti-endothelial cell antibodies (AECA), anti-cardiolipin antibodies (aCL) and serum mannose-binding lectin (MBL) profiles of a large cohort of Yemeni patients with rheumatic heart disease (RHD) and to correlate these findings with clinical features of the disease. Patients (n = 140) were recruited from Al-Thawra Hospital in Sana'a, Yemen. All had RHD diagnosed according to modified Jones' criteria. We also studied 140 sex- and age-matched healthy blood donors from the same area. Echocardiography was performed according to the recommendations of the American Society of Echocardiography. Solid phase enzyme-linked immunosorbent assays (ELISAs) were used to measure AECA and aCL titres and serum MBL levels. Forty per cent of the patients were AECA-positive, but only 7·8% were positive for aCL antibodies. Serum MBL levels were significantly lower in the RHD group (median 4221 ng/ml versus 5166 ng/ml in healthy controls). AECA titres were correlated positively with patient age, duration of RHD and the severity of aortic stenosis, as determined by echocardiographic findings. In several autoimmune rheumatic diseases, such as systemic lupus erythematosus, vasculitis and scleroderma, AECA have been shown to play pathogenic roles by producing proinflammatory and procoagulant effects (increased expression of adhesion molecules and tissue factors, increased cytokine release) in endothelial cells. In RHD, these autoantibodies might represent a pathological link between activation of the valvular endothelium and valvular damage. [source]