Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the clinical significance of IgG beta 2-glycoprotein I (GPI)-dependent anticardiolipin antibodies (aCL) in rheumatic diseases. Three hundred and seventeen patients were entered. They consisted of 133 patients with SLE, 60 with RA, 45 with SSc, 37 with PM, 23 with overlap syndrome (overlap), and 19 with unclassified connective tissue disease (UCTD). IgG beta 2-GPI-dependent aCL were examined by ELISA. While IgG beta 2-GPI-dependent aCL were detected in 13% of patients with SLE, these aCL were positive in two patients with SSc, two with overlap and 14 with UCTD. A significant association between IgG beta 2-GPI-dependent aCL and thrombosis was found. Clinical manifestations were studied in 32 patients with secondary APS based on SLE and 14 with primary APS (PAPS). Incidence of malar rash, arthritis, renal disorder, leucopenia, immunological disorders and hypocomplementemia were significantly less frequent in patients with PAPS. IgG beta 2-GPI-dependent aCL were detected in all patients with PAPS and in 34% of secondary APS. This difference was significant. These data suggest that IgG beta 2-dependent aCL are useful for identifying a subset in patients with APS.
Lupus 1995 Feb
PMID:Disease distribution of beta 2-glycoprotein I-dependent anticardiolipin antibodies in rheumatic diseases. 775 7

The mouse model described in this study offers a unique method of determining the characteristics and mechanism(s) of action of aCL antibodies in thrombosis in vivo. In addition, this animal model enables the study of the kinetics of formation and dissolution of thrombus, as well as clot area, to be studied in a dynamic fashion. Other models for evaluation of thrombus formation rely on measurements of thrombus size and weight in ligated vessel segments where flow may be interrupted artificially. In addition, two important findings can be extracted from the study. (1) The size of the thrombi were significantly larger in mice that were passively immunized with IgG-APS (four patient samples examined) and with IgM-APS (two patient samples examined) compared with mice injected with saline or with immunoglobulin from control patients. (2) The clot persisted significantly for longer periods of time (total time) in animals injected with IgG-APS or IgM-APS when compared with control animals. Based on in vitro experiments, it is possible that these antibodies may inhibit protein C activation, neutralize the inhibitory activity action of beta 2 glycoprotein I (beta 2GPI), or activate platelets at the site of the femoral vein injury. Because this model enables to study the dynamics of thrombus formation, it is possible that these hypotheses and other mechanisms by which aPL antibodies are thrombogenic be investigated. Future studies will also include the effects of different levels of antibodies, as well as effects of affinity purified and monoclonal aPL antibodies on thrombus formation.
Lupus 1994 Aug
PMID:Antiphospholipid antibodies in an in vivo thrombosis model in mice. 780 10

Although the APS seen as a PAPS or accompanying SLE essentially manifests the same clinical features, there appears to be distinct differences in the two groups of patients which have been summarized in this article. Additionally, the fact that some patients with Sneddon's syndrome, Trousseau's syndrome, or even Addison's disease, may in reality be examples of aPL-related vascular occlusive events has opened new avenues, not only for identification of these patients, but also for more systematic therapeutic regimens.
Lupus 1994 Aug
PMID:'Primary', 'secondary' and other variants of the antiphospholipid syndrome. 780 19

The class II and especially the DQB1 locus of MHC genes, as well as C4 deficiency alleles appear to be associated with genetic risk for developing aPL. The extensive linkage disequilibrium among some of these risk factors makes it difficult to assign a causal role for any of these alleles by means of previous population studies of patients with APS; studies a patients with primary APS, in particular, have involved relatively few patients. Although there appear to be some overall similarities between the known MHC associations of primary APS and those of secondary APS, only a modest relative risk of APS is associated with MHC alleles, as discussed above, and other unknown risk factors must also be important. Whether these unknown risk factors for primary APS are different from those in secondary APS is an area for further investigation. In addition, new genes continue to be identified in the MHC class II and III regions that appear to have important roles in antigen processing and recognition. Interethnic studies of these and other alleles in large cohorts would be informative since ethnic groups of African, Japanese or Caucasian backgrounds often exhibit differing allelic linkage disequilibria within the MHC. Studies of linkage relationships in various MHC haplotypes have, for example, helped to clarify the role of MHC class II oligo alleles in rheumatoid arthritis. Further clarification of the roles of these MHC alleles will also depend on functional studies in experimental models and in vitro, to assess the roles of these risk factors in aPL production. The roles of non-MHC risk factors and of environmental agents that are operative within families also warrant further studies.
Lupus 1996 Aug
PMID:Histocompatibility genes in antiphospholipid antibody syndrome. 886 95

Due to recent acquisitions, diagnostic criteria for the antiphospholipid/cofactors syndrome need to be improved. In the absence of a "common biological denominator", the best approach should be based on a scoring system mixing clinical and immunological items. APS might be composed of different biological subsets characterized by antibodies directed to various cofactors. Among clinical subsets, the categorization between "primary" and SLE-related APS may be difficult to achieve. Contrasting with the innumerable conditions associated with the presence of aPL, the diversity of "true" secondary APS should probably be restrained. Attempts at establishing correlations between clinical and biological APS subsets will require further studies.
Lupus 1996 Oct
PMID:1996 diagnostic and classification criteria for the antiphospholipid/cofactors syndrome: a "mission impossible'? 890 60

In 1990, three groups simultaneously reported that putative IgG antibodies to anionic phospholipids were either not directed to phospholipids or at least required beta 2-glycoprotein-I (beta 2-GP-I) for reactivity in vitro. During the same year, our group described a patient with "idiopathic' hemolytic anemia with serum and erythrocyte-bound IgM antibodies to phosphatidylcholine later found to be independent of beta 2-GP-I for antigen recognition. Lately, the field has been expanded considerably with: (1) the description of other potential antigens such as prothrombin for some lupus anticoagulants, (2) the finding of crossreactivity between some antiphospholipid antibodies (aPL) with thrombomodulin, (3) the presence of serum antibodies to beta 2-GP-I (anti-beta 2-GP-I) in patients with SLE and thromboses, (4) the findings that the clinical manifestations of APS in SLE patients associate more strongly with anti-beta 2-GP-I than with aPL, (5) our finding of a group of SLE patients with the clinical manifestations of APS, with negative serum aPL, but with positive anti-beta 2-GP-I, (6) the description of a group of patients with the clinical manifestations of APS, without serum aPL, without serological nor clinical evidence of any autoimmune disease, but with IgG anti-beta 2-GP-I, and (7) the observation that serum anti-phosphatidylethanolamine antibodies detected in some patients with APS require kininogen (alone or complexed with the kininogen-binding protein), prekallikrein and/or factor XI for in vitro reactivity. Thus, there are antibodies that may be considered true aPL; other "aPL' require a protein cofactor for their detection in vitro, at least in the case of beta 2-GP-I it would appear that their epitope is present on the protein proper not on the phospholipid, hence these are pseudo aPL, and a third group of related anti-cofactor autoantibodies that are directed to the protein in the absence of phospholipid. Clearly, the term "antiphospholipid syndrome' has become obsolete. We propose the term "Antiphospholipid/Cofactor Syndromes' to cull the various syndromes.
Lupus 1996 Oct
PMID:The concept and classification of antiphospholipid/cofactor syndromes. 890 61

Whether the vasculopathy in APS is thrombosis or vasculitis is more than a mere academic interest; the distinction is important not only for unravelling the pathogenesis of vascular injuries in APS but also for selecting the appropriate choice of drug treatment. A diagnosis of vasculitis would call for treatment with corticosteroids and cytotoxic agents which are not without serious side effects and drug toxicity. The same powerful but potentially dangerous drugs are clearly quite ineffectual in treating or preventing thrombosis associated with APS which has been known to respond in the lowly and inexpensive aspirin. The vasculopathy of APS remains almost exclusively thrombotic in nature according to our current state of knowledge, even if one were to accept capillaritis as a bona fide member in the family of vasculitides, the 'microangiitis'. Vasculitis secondary to an independent underlying disease, such as SLE, may coexist with APS in a patient. In the management of APS patients, the distinction between a true vasculitis coincidental with and one that is causally related to APS affects clinical decision making, and not just a matter of semantics or an academic curiosity. In vasculopathy of APS, thrombosis is the culprit and vasculitis, when present, is the consort. This is still true until newer and more convincing evidence emerges and proves to be contrary.
Lupus 1996 Oct
PMID:Vasculopathy of the antiphospholipid syndromes revisited: thrombosis is the culprit and vasculitis the consort. 890 62

The antiphospholipid syndrome may present itself to virtually all medical specialties. It can be as non-threatening as thrombophlebitis or mild thrombocytopenia or as severe as cerebral arterial infarct or the so called "catastrophic APS". In order to diagnose it properly, it is important to be aware of its clinical manifestations and laboratory peculiarities. The primary form of APS seems to be more common than the SLE related one. Because any artery or vein may be involved, the spectrum of clinical manifestations of APS is so wide that they include virtually all medical specialties.
Lupus 1996 Oct
PMID:Clinical manifestations of the aPL syndrome. 890 68

Utilizing this unique animal model of thrombosis we demonstrated that human (IgG, IgM or IgA) polyclonal and monoclonal antiphospholipid antibodies derived from APS patients have a significant enhancing effect on thrombus formation. This effect is reversed by treatment of the mice with hydroxychloroquine (plaquenil). In addition murine polyclonal and monoclonal anticardiolipin antibodies induced by active immunization with human beta 2-GP1 or human anticardiolipin antibodies showed to have thrombogenic properties in CD1 mice. Antibodies with antihuman beta 2-GP1 activity alone did not seem to affect thrombus formation.
Lupus 1996 Oct
PMID:In vivo models of thrombosis for the antiphospholipid syndrome. 890 80

During the last few years several murine models for APS have been described. These include spontaneous occurring disease, or APS induced by immunization with pathogenic autoantibodies. Employing those models, several treatment modalities, in different stages of the disease, were studied. Treatments which showed promising potential for application in patients with APS include immunomodulation with specific anti-idiotypic or anti-CD4 antibodies, treatment with IL-3, high-dose intravenous immunoglobulins, ciprofloxacin or bromocriptine, as well as antithrombotic and anticoagulant treatments using aspirin and/or low-molecular-weight heparin. Bone-marrow transplantation was also found to improve clinical and serological manifestations of the disease. These studies might promote the handling of controlled clinical trials assessing their efficacy in APS patients.
Lupus 1996 Oct
PMID:Immunomodulation of experimental APS: lessons from murine models. 890 82


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