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

Autoimmune diseases may be classified into two groups: autoantibody-mediated and cellular-mediated. In many autoimmune conditions the autoantigen is well-defined, immunogenic and, upon immunization of the naive animal, will lead to the production of autoantibodies and, eventually, to the induction of the respective autoimmune disease. However, in certain autoimmune diseases the autoantigen is either ill-defined, or is not immunogenic, or is intracellular. In many of these situations it is difficult to explain the emerging clinical findings by the mere binding of the autoantibody to the autoantigen. We herewith propose an additional mechanism for autoimmune disease induction, employing active idiotypic immunization. The induction of the disease is exemplified by three clinical models-SLE, APS, and Wegener's granulomatosis. The implications for human disease are discussed.
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PMID:Idiotypic induction of autoimmunity: do we need an autoantigen? 776 49

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.
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PMID:The concept and classification of antiphospholipid/cofactor syndromes. 890 61

Antiphospholipid (aPL) syndrome, or APS,--a cluster of conditions that includes arterial or venous thromboses and thrombocytopenia, as well as recurrent fetal loss associated with elevation of aPL antibody--has been reported to occur 2-5 times more frequently in women than men. Strong familial associations lead to the suspicion that aPL positivity, estimated to be present in 2% of the population, is a heritable trait in some cases. Currently, 2 major categories of the illness are recognized--primary and secondary. Secondary APS may be associated with autoimmune disease, malignancy, infectious disease, or drug-induced states. Two assays, one for lupus anticoagulant antibodies and the other for anticardiolipin (aCL) antibodies, are recognized to be the gold standards for serologic diagnosis of the disease. Despite extensive attempts at international standardization of aCL test results, no consensus exists for a value beyond which the test is considered positive. Interestingly, a "dose-effect" relationship for aCL antibody titers has been noted--higher titers of the antibody correlate with increased numbers of thrombotic events. An experimental assay for antibody against beta 2-glycoprotein 1 (beta-2-GP1), a phospholipid-binding protein, may become the most important assay for aPL. Skin findings in APS include livedo reticularis, ulceration, gangrene, or purpura, and, when present, may be the key to diagnosis of this sometimes insidious syndrome. Anticoagulation, usually with warfarin, is the mainstay of therapy, although steroids, immunosuppressive agents, hydroxychloroquine sulfate, and plasmapheresis may all be beneficial adjunctive therapy.
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PMID:Impact of the Antiphospholipid Syndrome: A Critical Coagulation Disorder in Women. 974 73

The clinical features of antiphospholipid (or Hughes') syndrome (APS) are most commonly seen in individuals who have raised levels of IgG anticardiolipin antibodies. Most murine models of the syndrome have involved the administration of such antibodies to normal mice. However, APS can occur in the presence of raised levels of serum IgM anticardiolipin antibodies alone. The present study was designed to see if an IgM monoclonal antibody can induce changes in mice similar to those seen in human APS. This antibody, BH1, has previously been derived from a patient with primary APS. In its ligand-binding and idiotypic characteristics it is representative of antiphospholipid antibodies (aPL) found in the serum of patients with APS. In order to minimise the immune response to human IgM, we used transgenic mice (F15) which express, and are predicted to be tolerant of, human immunoglobulin mu chains. The features of APS may develop more readily in individuals who have an existing autoimmune disorder, such as systemic lupus erythematosus (SLE). We therefore crossed these transgenic mice with New Zealand Black (NZB, SLE-prone) mice, and used the progeny (F15 x NZB/F1) in our experiments. Twenty-four F15 x NZB/F1 mice were given BH1, or a control IgM antibody, (A5566) immediately preceding and then three times during pregnancy. There was a reduction in the mean number of foetuses in animals given BH1 compared with those given A5566 (8.6 vs 11.0; P < 0.05), and a similar reduction in mean total foetal weight per pregnancy (9.05 vs 12.73 g; P < 0.05). Two mice showed a marked reduction in platelet count. No evidence of thrombosis was detected macroscopically or histologically. Our results show a lower incidence of APS-type features compared to previous studies in which mice have been administered aPL. This may be because BH1 is an IgM antibody. Nevertheless, the data support the concept that IgM aPL of particular ligand-binding specificities may have a direct pathogenetic role in certain cases of human APS.
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PMID:The effects of a human IgM monoclonal anticardiolipin antibody on pregnancy in a transgenic mouse model. 1134 Nov 6

We studied 99 patients with systemic autoimmune disease (5 males, 94 women; mean age 37 year, range 16-72): 28 Primary Antiphospholipid Syndrome, 67 Systemic lupus Erythematosus, 1 Mixed Connective Tissue Disease, 2 Undifferentiated Connective Tissue Disease and 1 Discoid Lupus. Based on the observation that native PT shows conformational changes in presence of Ca++ ions and discloses new epitopes available for binding with phospholipids, we performed 3 different methods for the detection of aPT in presence and absence of Ca++, finding a different incidence of specific autoantibodies, associated with clinical features of APS (aPT in presence of Ca++) or non associated (aPT in absence of Ca++). The presence of aPT was significantly associated also with the presence of Lupus Anticoagulant (LAC). The detection of aPT (in presence of Ca++) significantly enhances diagnostic sensibility of APS allowing the identification of a subset of patients (6/99) with clinical features of APS, but with negative LAC, aCL and a beta2-GPI; in fact (limited to thrombotic episodes) the sensibility rises from 56.2% with one test (LAC) to 81.1% with the application of LAC, aCL, a(beta)2GPI and aPT.
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PMID:[Role of anti-prothrombin in antiphospholipid syndrome]. 1240 33

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; APS-1) is an autosomal recessive autoimmune disease, caused by mutations in the AIRE (autoimmune regulator) gene. Due to the proposed role of AIRE in central immune tolerance, the immune investigation of four females diagnosed with APECED, their siblings, parents and 14 age-matched controls was performed. The parameters analyzed included immunoglobulins, autoantibodies, cellular immunity and production of cytokines IFNgamma, IL-4 and IL-10, reflecting Th1xTh2 balance. Low IFNgamma levels (455 +/- 191 pg/ml) were detected in all affected girls compared to controls (910 +/- 406 pg/ml). Two girls with homozygous R257X mutations showed similarly marked elevation of IgM and increase of CD3+CD4+ lymphocytes. Positive autoantibodies against smooth muscle were found in one affected girl; another girl and her mother had antibodies against gastric parietal cells. Interestingly, all fathers had dramatically elevated levels of IgA and activated T lymphocytes. High frequency of abnormal immune results among parents is a novel finding which might suggest a subclinical immune deficit in heterozygotes with AIRE mutations.
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PMID:Immunological findings in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and their family members: are heterozygotes subclinically affected? 1250 56

No significant differences were reported for the frequency of DR3-DQ2 and DR4-DQ8 haplotypes in a recent study of one of the largest cohorts worldwide of patients with isolated Addison's disease compared to patients with APS II. However, previous studies had suggested that the HLA-DQ genes, especially DQA1*0102, may be a genetic marker for resistance to autoimmune thyroid disease, which is the most frequent disease in APS II or III. Until now, HLA-DQA1 alleles have not been systematically investigated in APS. We determined the HLA-DR and HLA-DQA1 association in 112 unrelated patients with APS II (n = 29), APS III (n = 83) and 184 unrelated patients with single-component diseases without further manifestations of APS: Graves' disease (n = 70), Hashimoto's thyroiditis (n = 53), autoimmune Addison's disease (n = 15), vitiligo (n = 16) and alopecia (n = 30), and 72 healthy controls - German Caucasians - to identify possible predisposing and protective HLA class II alleles in APS. In agreement with previous studies, we detected a significantly higher frequency of DR 3 and/or DR 4 in patients with APS II and III compared to controls. In patients with APS II, we detected a significantly higher frequency of DQA1*0301 and *0501 compared to controls confirming the increased frequency of an extended HLA DRB1-*04-DQA1-*03-DQB-*03 haplotype as previously described. In contrast, only DQA1*0301 was increased in our patients with APS III compared to controls. Moreover, we detected an increased frequency of DQA1*0301 in patients with APS, whereas DQA1*0301 was only significantly elevated in alopecia in patients with single-component diseases without APS. Therefore, our results indicate an association between DQA1*0301 and APS II or III since this allele was otherwise not significantly associated with any of its component diseases except alopecia. Moreover, our data imply that the allele DQA1*0301 is a marker of increased risk for further APS manifestations in patients who suffer from an organ-specific autoimmune disease.
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PMID:HLA-DQA1*0301-associated susceptibility for autoimmune polyglandular syndrome type II and III. 1273 93

We have described a case of a rare autoimmune disease, called autoimmune polyglandular syndrome type I (APS type I), in a 44-year-old woman. APS type I is an autosomal recessively inherited disorder, connected with mutations in AIRE (autoimmune regulator) gene. Subsequently, autoantibodies directed towards tissue-specific enzymes are produced, which causes destruction of multiple tissues and organs, first of all--endocrine glands. In the described woman, primary hypoparathyroidism occurred in childhood. Addison disease, chronic candidiasis of the nails and vitiligo developed in adolescence. Before she was 30, a premature ovarian failure, and axilla and pubis alopecia occurred. The last recognized disorders were cholelithiasis and candidiasis of oesophagus. The late diagnosis resulted in numerous complications of the disease and the patient's life quality impairment.
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PMID:[Autoimmune multiglandular syndrome type I--a case study]. 1577 Nov 37

Antiphospholipid syndrome (APS, Hughes' syndrome) is a systemic autoimmune disorder characterized by arterial and/or venous thrombosis and recurrent foetal loss, accompanied by mild to moderate thrombocytopaenia and elevated titres of antiphospholipid antibodies (aPLs): lupus anticoagulant (LAC) and/or anticardiolipin (aCL) antibodies. APS was defined originally in 1983 in systemic lupus erythematosus (SLE) patients, but later it was found that APS can be primary or secondary to other autoimmune diseases or malignancy. During the past 20 years many organs have been reported to be involved in this syndrome and the clinical manifestations are seen in every medical field. Moreover, many aPLs have been found in APS besides aCLs and LACs, which bind to the autoantigen beta-2-glycoprotein I (beta2GPI). Treatment for APS, based on antiplatelet and anticoagulation drugs, is dependent on various parameters, including whether SLE is also present, classical vs non-classical manifestations of the diseases, women with APS based on pregnancy morbidity, the presence of elevated aCL antibody titres in the absence of clinical manifestations, and catastrophic APS.
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PMID:The systemic nature of the antiphospholipid syndrome. 1579 93

APS is rare in the pediatric age, but it represents an interesting phenomenon because most of the known "second hit" risk factors such as atherosclerosis, smoking, hypertension, contraceptive hormonal treatment, and pregnancy are not present in childhood. This could also be the reason for the prevalence of some clinical manifestations rather than others in PAPS. On the other hand, the increased frequency of infectious processes in the childhood age is likely responsible for the relatively high prevalence of non-pathogenic and transient aPL. Such points raise the problem of a different diagnosis or monitoring approach in pediatric APS. Of particular interest is the special entity of neonatal APS, which represents an in vivo model of acquired autoimmune disease, in which transplacentally acquired aPL cause thrombosis in the newborn. International registries for pediatric and neonatal APS are currently in place; epidemiologic, clinical, and laboratory re-search will help to shed light on all the still obscure aspects of this fascinating but rare disorder in the very young. Finally, treatment is less aggressive overall in pediatric APS, given the reluctance to anticoagulate children over the long term. Studies on the outcome of pediatric APS and the relative risks of prolonged anticoagulation in children are necessary to determine the type and duration of anticoagulation therapy.
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PMID:Pediatric antiphospholipid syndrome. 1688 84


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