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Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animal models of the relatively new antiphospholipid syndrome (APS) enabled researchers to understand disease pathogenesis and to test novel experimental therapeutic modalities. Animal models of APS include spontaneous genetic models and experimental induced models. The latter test more reliably the pathogenicity of antiphospholipid antibodies because the syndrome is induced in normal mice rather than being secondary to a preexisting autoimmune disease. Reports about animal models of APS in the recent year provide new insights into the pathogenesis of antiphospholipid antibodies and beta2-glycoprotein-I in reproductive failure, neurologic manifestations, thrombosis, and atherosclerosis. In addition, novel therapies that were successful in experimental APS included anti-idiotypes, oral tolerance, and specific peptides that bind to beta2-glycoprotein-I. Animal models provide the first step in development of novel therapies for patients with APS.
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PMID:Antiphospholipid syndrome: insights from animal models. 1096 84

This paper examines the methodology of anti-beta(2)-glycoprotein I (beta(2)-GPI) epitope determination and provides further epitope studies using human sera containing anti-beta(2)-GPI autoantibodies. Studies in this field may be misleading as the antigen coating density using mutant forms of beta(2)-GPI may be below the threshold required for monogamous divalent binding by low affinity anti-beta(2)-GPI autoantibodies, while being easily detected by high affinity anti-beta(2)-GPI from immunized animals. The antigen density threshold effect is found in anti-beta(2)-GPI autoantibodies from humans and from monoclonal anti-beta(2)-GPI derived from mice with models of autoimmune disease. Anti-beta(2)-GPI from an autoimmune mouse and from 18/21 human sera did not bind above background levels to a domain-I-deleted mutant. In addition, single point mutations in domain I result in dramatic changes in the binding of many human sera containing anti-beta(2)-GPI. These findings support a conclusion that domain I of beta(2)-GPI contains significant epitopes for the anti-beta(2)-GPI antibodies found in the antiphospholipid syndrome.
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PMID:Epitope studies with anti-beta 2-glycoprotein I antibodies from autoantibody and immunized sources. 1096 91

Infertility affects 10-15% of all married couples of reproductive age in the United States and results in substantial emotional distress and medical investment. Though it is uncertain whether antiphospholipid syndrome (APS) is a cause of infertility, inevitably there is a small proportion of women who have both APS and infertility. In turn, some of these patients are candidates for ovulation induction, with or without assisted reproductive technologies, such as in vitro fertilization and embryo transfer, in an attempt to achieve successful pregnancy. The medications used for ovulation induction cause an increase in ovarian estrogen production beyond that typical of a normal menstrual cycle. Clinicians are appropriately concerned about the potential adverse effects of this estrogen surge on the clinical status of women with autoimmune disease. For APS, a primary concern would be that of thrombosis or embolism.
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PMID:Management of patients with antiphospholipid antibodies undergoing in vitro fertilization. 1096 11

Antiphospholipid syndrome (APS) is a disease characterized by venous and arterial thromboses or spontaneous abortions and the repeated detection of antiphospholipid antibodies (aPL). APS may be associated with another autoimmune disease (secondary APS), particularly systemic lupus erythematosus (SLE), or unrelated to an underlying disease (primary APS). APS affects almost all organs. In addition to the clinical criteria, lupus anticoagulant testing and immunological aPL determinations are required to establish the diagnosis of APS.
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PMID:Antiphospholipid syndrome. 1101 73

Contrary to infective anticardiolipin (aCL) antibodies, autoimmune aCL antibodies react with phospholipids (PL) mainly via binding to the plasma glycoprotein cofactor beta2-Glycoprotein I (beta2GPI). While there is a well-documented link between the risk of thrombosis and the presence of beta2GPI-dependent anticardiolipin antibodies, the pathological impact of other antiphospholipid antibodies is less clear. By means of cardiolipin affinity-chromatography, we isolated and identified 3 CL-binding proteins, complement component C4, complement factor H and a kallikrein-sensitive glycoprotein, and tested for the presence of autoantibodies against these proteins in patients with antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and other autoimmune diseases. High titers of autoantibodies to C4 as compared to age- and sex-matched healthy controls were present in 3 of 26 patients with APS, and weak titers were found in 2 of 26 patients with SLE and in none of 26 patients with other autoimmune diseases. Autoantibodies to complement factor H were found in 4 APS, 3 SLE and none of the other autoimmune patients. Autoantibodies to kallikrein-sensitive glycoprotein were detected in 6 APS patients, 1 SLE patient, and 1 patient with another autoimmune disease. A close relationship between these antibodies was found, suggesting their origin from a common macromolecular complex. However, no relationship with anti-beta2GPI antibodies was found, with the three patients with higher levels of autoantibodies having a low titer of anti-beta2GPI antibodies. In conclusion, some patients with APS harbor circulating antibodies to other CL-binding proteins which might be useful to further characterize these patients.
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PMID:Some patients with antiphospholipid syndrome express hitherto undescribed antibodies to cardiolipin-binding proteins. 1120 89

Antiphospholipid antibodies (aPLs) are associated with arterial and venous thrombosis, recurrent pregnancy loss and thrombocytopenia. Although aPLs have not yet been conclusively shown to be causal in thrombosis and miscarriage, they are useful laboratory markers for the antiphospholipid syndrome (APS). The syndrome can complicate another autoimmune disease, most commonly systemic lupus erythematosus, but more often occurs alone -- primary APS. Identification of the syndrome is clinically important because of the risk of recurrent thrombosis and the need for antithrombotic therapy in many cases. Diagnosis and treatment of APS represent significant challenges, however, owing to the protean clinical manifestations and associations, limitations of currently available laboratory tests for aPLs, and the lack of clear evidence-based guidance on optimal management.
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PMID:Antiphospholipid syndrome: state of the art with emphasis on laboratory evaluation. 1125 37

Autoimmune disease-associated lymphadenopathy shows marked histopathological and clinical diversity. We describe the clinicopathological and immunohistochemical findings of nine cases of autoimmune disease-associated lymphadenopathy, which posed a serious differential diagnostic problem regarding T-zone dysplasia with hyperplastic follicles. There were two males and seven females aged 25 to 65 years (median 37 years). The patients had multicentric lymphadenopathy in association with clinical and laboratory findings suggestive of an "autoimmune disease". Four patients were diagnosed to have systemic lupus erythematosus (SLE), and the remaining five patients had antiphospholipid antibody syndrome and Sjogren's syndrome (SS), rheumatoid arthritis (RA), chronic thyroiditis, RA and SS, and SLE and SS, respectively. None of the nine patients developed malignant lymphomas during the follow-up periods from 44 to 225 months (median 103 months). The lesions were characterized by paracortical hyperplasia with prominent vascular proliferation and many lymphoid follicles with germinal centers. The paracortical area usually contained numerous small T-lymphocytes without cytological atypia, accompanied by a variable number of plasma cells, B-immunoblasts, and histiocytes. Polymerase chain reaction analysis demonstrated no clonal rearrangement of the T-cell receptor chain gene in four cases examined, although immunoglobulin heavy chain rearrangement was detected in only one case. These findings suggest that autoimmune disease-associated lymphadenopathy, especially SLE, shares the histological features with T-zone dysplasia with hyperplastic follicles. The nine cases presented here should be differentiated from T-zone lymphoma with follicles and angioimmunoblastic lymphoma with hyperplastic germinal centers. To avoid overdiagnosis and overtreatment, we emphasize the need to turn attention to these clinical and laboratory findings as well as to the morphological features.
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PMID:Autoimmune disease-associated lymphadenopathy with histological appearance of T-zone dysplasia with hyperplastic follicles. A clinicopathological analysis of nine cases. 1135 9

The antiphospholipid syndrome is characterized by arterial and venous thrombosis, as well as pregnancy morbidity, in the presence of elevated levels of antiphospholipid antibodies. These autoantibodies have procoagulant activity, as they affect platelets, humoral coagulation factors, and endothelial cells. In addition, they are proatherogenic, as demonstrated by animal models and by the increased prevalence of cardiovascular diseases in patients with systemic lupus erythematosus and antiphospholipid syndrome. Moreover, antiphospholipid antibodies, including anticardiolipin, anti-b2-glycoprotein-I, and anti-oxidized low-density lipoprotein, are associated with atherosclerosis and its consequences in the general population as well. This autoimmune aspect of atherosclerosis in the presence or absence of an autoimmune disease suggests benefit from development of immunomodulating therapies.
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PMID:Antiphospholipid syndrome, antiphospholipid antibodies, and atherosclerosis. 1138 99

Antiphospholipid syndrome (APS) is an autoimmune disorder in which antiphospholipid antibodies (aPL) are thought to be involved in the development of venous and/or arterial thrombosis. APL found in this syndrome are antibodies directed against a variety of phospholipid (PL) binding-proteins of which beta3-glycoprotein I (beta2GPI) and prothrombin are considered to be the major antigens. Some of these antibodies prolong PL-dependent clotting reactions and are termed lupus anticoagulants (LA). Autoimmune aPL which bind through beta2GPI to cardiolipin are called anticardiolipin antibodies (aCL). Clinical studies indicate that LA is a stronger risk factor for thrombosis than aCL. The production of monoclonal antibodies against beta2GPI and prothrombin has enabled us to understand the mechanism by which LA prolong coagulation in vitro. LA form bivalent antigen-antibody complexes with increased affinity for PL which compete with coagulation factors for the same catalytic surface. These LA positive monoclonal antibodies may be helpful in further improving the laboratory diagnosis of LA.
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PMID:Antiphospholipid syndrome: diagnostic aspects of lupus anticoagulants. 1148 46

Antiphospholipid syndrome is a rate systemic autoimmune disease characterized by widespread arterial and venous thrombosis, recurrent abortion and thrombocytopenia. Laboratory tests reveal antibodies against phospholipids. These antibodies are detected by functional tests for the lupus anticoagulant, the anticardiolipin ELISA, the anti-beta 2-glycoprotein 1 ELISA and ELISA tests for antibodies against other cofactors and phospholipids. Pathogenetic mechanisms of thrombosis are poorly understood. Diagnostic assays for detection of antiphospholipid have not been yet adequately standardized.
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PMID:[The antiphospholipid syndrome and antiphospholipid antibodies]. 1156 67


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