Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The increasing prevalence with age of antiphospholipid antibodies (aPL), of dementia and of stroke complicates the study of a causal relationship between antiphospholipid syndrome (APS) and dementia. Prolonged aPTT due to circulating anticoagulants (CAC) may serve as a more specific laboratory marker of APS. In a hospital-based study, we examined all patients with CAC and included 23 who fulfilled standard criteria for primary APS. These patients were assessed for dementia, vascular brain disease, autoimmune disease activity and dementia risk factors. Among CAC-positive APS patients, 13 of the 23 (56%) were demented and these were significantly older (mean age+/-S.E., 68+/-3 years) than the nondemented APS group (n=10, 51+/-4 years; p<0.01, Student's t-test). The demented patients had significantly more pathology on computerized brain tomography (CT) and electroencephalography (EEG) studies but six of them had no clinical or CT evidence of vascular brain disease. Erythrocyte sedimentation rate was significantly lower in the dementia group, in which there was also a significant negative correlation between levels of aPL and age. CAC-positive APS patients seem to be at risk for developing dementia with age, suggesting a pathogenic role for prolonged exposure to elevated aPL.
 ...
PMID:Prevalence and clinical features of dementia associated with the antiphospholipid syndrome and circulating anticoagulants. 1241 62

Antiphospholipid antibody syndrome is an acquired autoimmune disorder characterized by vascular thrombosis and/or recurrent pregnancy losses along with laboratory evidence of antiphospholipid antibodies. Anticoagulation rather than immunosuppression is the mainstay of treatment. Despite the effectiveness of oral anticoagulation for the prevention of recurrent thromboembolic episodes, thrombotic complications in the setting of apparently therapeutic oral anticoagulation have been observed; this may at times be due to difficulties in maintaining a consistently therapeutic level of anticoagulation. Low-molecular-weight heparin has been a useful alternative for long-term anticoagulation when there is difficulty in managing oral anticoagulant therapy and has the advantage of a consistent anticoagulant effect. In this report, we describe a woman with primary antiphospholipid antibody syndrome who developed extensive pulmonary embolism despite receiving a proven therapeutic dosage of low molecular weight heparin.
 ...
PMID:Low-molecular weight heparin: treatment failure in a patient with primary antiphospholipid antibody syndrome. 1244 50

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the persistent presence of antiphospholipid antibodies (aPLs) and recurrent thrombosis or fetal loss. The thrombophilic state has been partially related to the induction of a proinflammatory and procoagulant endothelial cell (EC) phenotype induced by anti-beta(2)-glycoprotein I (beta(2)-GPI) antibodies that bind beta(2)-GPI expressed on the EC surface. Anti-beta(2)-GPI antibody binding has been shown to induce nuclear factor-kappa B (NF-kappa B) translocation leading to a proinflammatory EC phenotype similar to that elicited by interaction with microbial products (lipopolysaccharide [LPS]) and proinflammatory cytokines (interleukin 1 beta [IL-1 beta], tumor necrosis factor alpha [TNF-alpha]). However, the upstream signaling events are not characterized yet. To investigate the endothelial signaling cascade activated by anti-beta(2)-GPI antibodies, we transiently cotransfected immortalized human microvascular endothelial cells (HMEC-1) with dominant-negative constructs of different components of the pathway (Delta TRAF2, Delta TRAF6, Delta MyD88) together with reporter genes (NF-kappa B luciferase and pCMV-beta-galactosidase). Results showed that both human anti-beta(2)-GPI IgM monoclonal antibodies as well as polyclonal affinity-purified anti-beta(2)-GPI IgG display a signaling cascade comparable to that activated by LPS or IL-1. Delta TRAF6 and Delta MyD88 significantly abrogate antibody-induced as well as IL-1- or LPS-induced NF-kappa B activation, whereas Delta TRAF2 (involved in NF-kappa B activation by TNF) does not affect it. Moreover, anti- beta(2)-GPI antibodies and LPS followed the same time kinetic of IL-1 receptor-activated kinase (IRAK) phosphorylation, suggesting an involvement of the toll-like receptor (TLR) family. Our findings demonstrate that anti-beta(2)-GPI antibodies react with their antigen likely associated to a member of the TLR/IL-1 receptor family on the EC surface and directly induce activation.
 ...
PMID:Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies. 1253 7

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder affecting multiple organ systems. Treatment of the disease has contributed dramatically in the long-term survival of the patients and now SLE has become a chronic inflammatory disorder. Present data suggest 5, 10 and 20-year survival rates of 93%, 85% and 68% respectively. Accelerated atherosclerosis and early coronary artery disease have become important causes of death and hospitalisation in SLE patients. Many cardiovascular risk factors can be considered: disease activity (particularly kidney involvement), sedentary life (in nearly 70% of the patients), hyperlipidemia, antiphospholipid antibodies, serum homocysteine and many others. Although traditional risk factors are operative in patients with SLE, the risk for myocardial infarction was increased 8.3 folds after controlling these factors in a study, suggesting that SLE itself was the strongest risk factor for cardiovascular disease. Lipid abnormalities may play a major role in increasing cardiovascular risk in SLE patients who are characterized by elevated triglycerides, very low-density lipoprotein cholesterol (VLDL-C), reduced levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A-1. Anticardioli-pin antibodies may influence lipid levels in SLE; in particular SLE patients with IgG anticardiolipin antibodies had significantly lower HDL-C compared with patients with no anticardiolipin antibodies. Elevation of serum homocysteine is observed in 15% of SLE patients and is significantly associated with the development of stroke and arterial thrombotic events. The antiphospholipid syndrome (APS) is an acquired thrombotic disorder characterised by recurrent venous or arterial thrombosis or recurrent miscarriages, or both, associated with the presence in the serum of IgG or IgM anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC). APS may occur as a primary disorder (PAPS) or associated with connective tissue diseases, mainly systemic lupus erythematosus (secondary APS). Primary and secondary APS are both associated with a significant increase of cardiovascular risk.
 ...
PMID:[Cardiovascular risk factors in systemic lupus erythematosus and in antiphospholipid syndrome]. 1285 54

Ischaemic stroke is the only neurological manifestation accepted as a clinical diagnostic criterion for the antiphospholipid syndrome (APS). This association is reasonably well established in patients first diagnosed with APS but is less clear in randomly selected stroke patients who test positive on one occasion for antiphospholipid antibodies and who have no other evidence of systemic autoimmune disease. We propose a grading system that posits stroke to be definitely, likely or possibly associated with antiphospholipid antibodies (aPL). Further, there are limited prospective data to determine appropriate treatment. There is controversy as to whether the presence of aPL even increases risk of a recurrent stroke or other thromboembolic event, although data point to persistent medium-high titre aCL and/or LA as risk factors for recurrence. In the absence of data to guide clinicians on the best treatment, we cannot make strong recommnendations as to optimal therapy, nor can we propose clear consensus treatment guidelines.
 ...
PMID:Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002. 1289 89

Regulation of blood vessels is intrinsically tied to inflammatory signaling. Recent research suggests that chronic inflammation is associated with atherosclerosis risk. The antiphospholipid syndrome is a prototypic autoimmune disease. Disturbance of blood vessel homeostasis in this disorder may increase risk for atherosclerosis by mechanisms that are direct (through antibody targeting of blood vessel-regulating proteins) or indirect (via inflammatory mechanisms that have recently been implicated in autoantibody-mediated thrombosis).
 ...
PMID:The antiphospholipid syndrome and atherosclerosis: clue to pathogenesis. 1296 28

Hughes' syndrome, or antiphospholipid syndrome, is thought to be the cause of one in four strokes in people aged less than 40 years. It is an antiinflammatory autoimmune disorder in which the blood has a tendency to clot too quickly. It can affect any artery or vein in the body and the main symptoms are thrombosis, pregnancy loss and the presence of antibodies. If detected it can be treated effectively.
 ...
PMID:A guide to Hughes' syndrome. 1451 62

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL). Its etiology is linked to genetic predisposition, which is accounted for, at least in part, by genes of major histocompatibility complex (HLA system). The association of APS with human leukocyte antigen (HLA) alleles is a consequence of the association of aPL with HLA alleles. Some HLA alleles carry the risk to produce aPL, and this is independent of the clinical context. In fact, we find the same associations between HLA and aPL in primary APS and in APS secondary to systemic lupus erythematosus (SLE). The association of HLA-DR4, -DR7, -DRw53 and -DQB1*0302 with aCL that has been demonstrated in primary APS can also be found in SLE, a disease with a completely different pattern of HLA allele association (DR2, DR3, DRw52). In addition, the various aPL (anticardiolipin antibodies, lupus anticoagulant, anti-beta2GPI antibodies, antiphosphatidylserine/prothrombin antibodies) show similar HLA association, again independent of the clinical context (primary APS or SLE), and across various ethnic groups.
 ...
PMID:HLA class II alleles and genetic predisposition to the antiphospholipid syndrome. 1455 Aug 81

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbances in innate and adaptive immune mechanisms. Multiple systems and organs may be involved. Tissue damage and dysfunction are mediated by autoantibodies and immune complex formation. The lungs are among the organ systems commonly involved. The pulmonary manifestations usually occur in patients with multisystem disease and include: pleural involvement, parenchymal disease, pulmonary vascular disease and diaphragmatic dysfunction. Manifestations may range from sub-clinical abnormalities to life threatening disorders. Many of the pulmonary manifestations characteristic of SLE are seen in the antiphospholipid syndrome (APS) as well, in both the primary and secondary syndrome. In this review the diverse pulmonary manifestations are described as well as the diagnostic modalities available, including the use of induced sputum evaluation for early diagnosis and follow up. New treatment modalities are referred to.
 ...
PMID:Pulmonary disease in systemic lupus erythematosus and the antiphospholpid syndrome. 1487 52

Antiphospholipid antibodies represent a heterogeneous group of autoantibodies directed against anionic phospholipids (PLs) usually linked to protein cofactors. Their presence during the antiphospholipid syndrome is associated with risks of thrombosis and fetal losses. Among 5 randomly selected monoclonal antiphospholipid antibodies, all originating from a single patient suffering from this autoimmune disease, only 1 induced fetal losses when passively injected into pregnant mice. Its antiphospholipid activity was dependent on annexin A5, and its variable regions contained mainly 3 replacement mutations. To clarify the role of these mutations in the pathogenicity of the antibody, they were in vitro reverted to the germ line configuration. The resulting "germ line" antibody reacted with multiple self-antigens and only partially lost its reactivity against PLs, but it was no more dependent on annexin A5 and, more importantly, was no more pathogenic. This study illustrates that the in vivo antigen-driven maturation process of natural autoreactive B cells can be responsible for pathogenicity.
 ...
PMID:Pathogenic antiphospholipid antibody: an antigen-selected needle in a haystack. 1516 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>