Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using Chinese hamster ovary (CHO) cells that express high numbers of TSH receptor (TSHR) on their surface, we studied the feasibility of detecting directly by flow cytometry the binding of autoantibodies in patients' sera to the native TSHR. After using a serum (BBI) with high potency in the TSH binding inhibition (TBI) assay to establish the protocol, we studied an additional 38 sera: 10 without TBI activity (1-4.2% inhibition), 10 with moderately high TBI values (17.3-39.4% inhibition), 10 with high TBI levels (52-95.1% inhibition), 4 from normal individuals without autoimmune thyroid disease, and 4 from patients with systemic lupus erythematosus. We observed that a number of sera, including some without thyroid autoantibodies, contain antibodies against unknown antigens on CHO cells. Preadsorption with untransfected CHO cells before addition to the TSHR-10,000 cells eliminated or greatly reduced this nonspecific background. None of the sera from normal individuals, subjects with negative TBI values, or patients with systemic autoimmunity generated a positive signal on flow cytometry with TSHR-10,000 cells relative to the signal on untransfected cells. Remarkably, only 4 of 21 TBI-positive sera (including BBI) unequivocally recognized the TSHR on flow cytometry. In contrast, when thyroid peroxidase (TPO) autoantibodies in the same sera were studied using CHO cells overexpressing TPO on their surface, all 20 sera with TPO autoantibodies clearly elicited positive net fluorescence relative to untransfected cells. Study of the potent serum, BBI, revealed similar fluorescence (approximately 250 U) for TPO autoantibodies and TSHR autoantibodies at dilutions of 1:1000 and 1:10, respectively. Thus, by flow cytometry, the titer of TPO autoantibodies in the BBI serum is about 100-fold higher than that for TSHR autoantibodies in the same serum. In conclusion, the present data provide the strongest support for the idea that TSHR autoantibodies in the sera of patients with autoimmune thyroid disease are present at much lower levels than are TPO autoantibodies. This finding has important implications for the diagnostic detection of TSHR autoantibodies and for understanding the pathogenesis of Graves' disease.
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PMID:Thyrotropin receptor autoantibodies in serum are present at much lower levels than thyroid peroxidase autoantibodies: analysis by flow cytometry. 902 44

A patient with a history of recurrent late fetal loss associated with multiple placental infarcts and cerebrovascular ischemia at the age of 36, followed a year later by a myocardial infarction, was referred for further investigation. Coronary angiography was normal. Antinuclear factor, lupus anticoagulant, anticardiolipin antibodies, and other thrombophilia parameters were negative, but there was moderate hyperthyroidism with positive thyroid peroxidase antibodies. Platelet numbers and von Willebrand factor (vWF) were normal. Her platelets showed spontaneous aggregation that disappeared with aspirin intake. However, aggregation still was induced by low levels of ristocetin (0.3 to 0.5 mg/mL). The low-dose ristocetin aggregation in patient platelet-rich plasma (PRP) was completely blocked by neutralizing antiglycoprotein Ib (GPIb) and anti-vWF antibodies. The monoclonal anti-Fc gamma RII receptor antibody IV.3 inhibited partly, which suggests that PRP aggregation by low-dose ristocetin was elicited by vWF-immunoglobulin (Ig) complexes. Upon addition to washed human platelets, with vWF (10 micrograms/mL), purified patient Igs dose-dependently enhanced ristocetin (0.15 mg/mL)-induced aggregation between 0 and 500 micrograms/mL, an effect that disappeared again above 1 mg/mL. Aggregation was dependent on the vWF concentration and was blocked by IV.3 or neutralizing anti-GPIb or anti-vWF antibodies. The spontaneous aggregation of normal platelets resuspended in patient plasma could be inhibited totally by IV.3 and partially by neutralizing anti-GPIb or anti-vWF antibodies. Perfusion with normal anticoagulated blood, enriched with 10% of control or patient plasma, over surfaces coated with vWF showed increased platelet adhesion and activation in the presence of patient antibodies. Treatment of the patient with the antithyroid drug thiamazol and temporary corticosteroids, aspirin, and ticlopidine did not correct the platelet hypersensitivity to ristocetin. These observations suggest that some autoantibodies to vWF may both enhance vWF binding to platelets and cause platelet activation through binding to the Fc gamma RII receptor, and thereby may be responsible for a new form of antibody-mediated thrombosis.
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PMID:Recurrent arterial thrombosis linked to autoimmune antibodies enhancing von Willebrand factor binding to platelets and inducing Fc gamma RII receptor-mediated platelet activation. 953 91

The association of immune dysfunction in patients with human immunodeficiency virus (HIV) infection and AIDS and the development of autoimmune diseases is intriguing. Yet, the spectrum of reported autoimmune phenomena in these patients is increasing. An infectious trigger for immune activation is one of the postulated mechanisms and derives from molecular mimicry. During frank loss of immunocompetence, autoimmune diseases that are predominantly T cell subtype CD8 driven predominate. There is evidence for B cell stimulation and many autoantibodies are reported in HIV patients. We propose a staging of autoimmune manifestations related to HIV/AIDS manifestations and the total CD4 count and viral load that may be beneficial in identifying the type of autoimmune disease and establishing the proper therapy. In stage I there is the acute HIV infection, and the immune system is intact. In this stage, autoimmune diseases may develop. Stage II describes the quiescent period without overt manifestations of AIDS. However, there is a declining CD4 count indicative of some immunosuppression. Autoimmune diseases are not found. During stage III there is immunosuppression with a low CD4 count and the development of AIDS. CD8 T cells predominant and diseases such as psoriasis and diffuse immune lymphocytic syndrome (similar to Sjogren's syndrome) may present or even be the initial manifestation of AIDS. Also during this stage no autoimmune diseases are found. In stage IV there is restoration of immune competence following highly active anti-retroviral therapy (HAART). In this setting, there is a resurgence of autoimmune diseases. The frequency of reported rheumatological syndromes in HIV-infected patients ranges from 1 to 60%. The list of reported autoimmune diseases in HIV/AIDS include systemic lupus erythematosus, anti-phospholipid syndrome, vasculitis, primary biliary cirrhosis, polymyosits, Graves' disease, and idiopathic thrombocytopenic purpura. Also, there is an array of autoantibodies reported in HIV/AIDS patients which include anti-cardiolipin, anti-beta2 GPI, anti-DNA, anti-small nuclear ribonucleoproteins (snRNP), anti-thyroglobulin, anti-thyroid peroxidase, anti-myosin, and anti-erythropoietin antibodies. The association of autoantibodies in HIV-infected patients to clinical autoimmune disease is yet to be established. With the upsurge of HAART, the incidence of autoimmune diseases in HIV-infected patients is increasing. In this review, we describe the various autoimmune diseases that develop in HIV/AIDS patients through possible mechanisms related to immune activation.
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PMID:HIV and autoimmunity. 1284 88

Autoimmune thyroid disease (AITD) is the most common organ specific autoimmune disorder usually resulting in dysfunction (hyperfunction, hypofunction or both) of the thyroid gland. The syndromes comprising autoimmune thyroid disease are many intimately related illnesses: Graves' disease with goitre, hyperthyroidism and, in many patients, associated ophthalmopathy, Hashimoto's thyroiditis with goitre and euthyroidism or hypothyroidism but also thyroid dysfunction occurring independently of pregnancy and in 5-6% of postpartum women and thyroiditides induced by different drugs and other environmental influences. The immunological mechanisms involved in these diseases are closely related, while the phenotypes probably differ because of the specific type of immunological response that occurs. The syndromes are connected together by their similar thyroid pathology, similar immune mechanisms, co-occurrence in family groups, and transition from one clinical picture to another within the same individual over time. In some patients, other organ specific and nonorgan specific autoimmune syndromes are associated with autoimmune thyroid disease, including pernicious anemia, vitiligo, myasthenia gravis, primary adrenal autoimmune disease, celiac disease, rheumatoid arthritis or lupus. Thyroid peroxydase, TPO, the primary enzyme involved in thyroid hormonogenesis, was initially identified in 1959 as the 'thyroid microsomal antigenn. It is uncertain whether TPO autoantibodies or TPO-specific T cells are the primary cause of thyroid inflammation, which can lead, in some individuals, to thyroid failure and hypothyroidism. TPOAbs are the hallmark of AITB and are present in almost all patients with Hashimoto's thyroiditis, in two-thirds of patients with postpartum thyroiditis and also in 75% of patients with Graves' hyperthyroidism. The antibodies are mainly produced by lymphocytic infiltrate in the thyroid gland and only to a small extent by regional lymph nodes or the bone marrow. Unlike antibodies against thyroglobulin (Tg), TPO antibodies are capable of inducing antibody-dependent cell-mediated cytotoxicity. Antibodies to TSH-R mimic the function of TSH, and cause disease by binding to the TSH-R and stimulating (or inhibiting) thyroid cells. The TSHR, a member of the G protein-coupled receptor family with seven membrane-spanning segments. Patients with autoimmune thyroid disease may have both stimulating and blocking antibodies in their sera, the clinical picture being the result of the relative potency of each species; blocking antibodies seem more common in Graves' patients with ophthalmopathy compared to those without this complication. The major T cell epitopes are heterogeneous and T cell reactivity against certain TSH-R epitopes has been present in high proportion in normal subjects. More diversified response to TSH-R, with heterogeneity of epitope recognition by TSAb, is predictive of likely remission after antithyroid drug treatment for Graves' disease.
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PMID:[Diagnosis of autoimmune thyroid disease]. 1640 53

The interrelationship between prolactin (PRL) and the immune system have been elucitaded in the last decade, opening new important horizons in the field of the immunoendocrinology. PRL is secreted not only by anterior pituitary gland but also by many extrapituitary sites including the immune cells. The endocrine/paracrine PRL has been shown to stimulate the immune cells by binding to PRL receptors. Increased PRL levels, frequently described in autoimmune diseases, could depend on the enhancement of coordinated bi-directional communications between PRL and the immune system observed in these diseases. Hyperprolactinemia has been described in the active phase of some non organ-specific autoimmune diseases, as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and organ-specific autoimmune diseases, as celiac disease, type 1 diabetes mellitus, Addison's disease, autoimmune thyroid diseases. In these diseases PRL increases the syntesis of IFNgamma and IL-2 by Th1 lymphocytes. Moreover, PRL activates Th2 lymphocytes with autoantibody production. Of particular interest is the association between hyperprolactinemia and levels of anti DNA antibodies, islet cell antibodies (ICA), thyreoglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb), adrenocortical antibodies (ACA), transglutaminase antibodies (tTGAb) in SLE, in type 1 diabetes mellitus, in Hashimoto's thyroiditis, in Addison's disease and in celiac disease, respectively. High levels of PRL have been also frequently detected in patients with lymphocytic hypophysitis (LYH). Several mechanisms have been invoked to explain the hyperprolactinemia in LYH. The PRL increase could be secondary to the inflammatory process of the pituitary gland but, on the other hand, this increase could have a role in enhancing the activity of the immune process in LYH. Moreover, the detection of antipituitary antibodies targeting PRL-secreting cells in some patients with idiopathic hyperprolactinemia suggests the occurrence of a possible silent LYH in these patients. Finally, the role of anti-prolactinemic drugs to inactivate the immune process in LYH is still discussed.
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PMID:Prolactin and autoimmunity. 1641 Oct 65

To determine the patterns of thyroid dysfunction and autoantibodies associated with SLE and RA patients, twenty patients with SLE and another group of twenty with RA were studied. The results were compared with those of twenty apparently healthy age- and sex- matched controls. All patients were subjected to complete history taking, thorough clinical examination and joint examination. All patients and controls were subjected to the following investigations: T3, T4, TSH, antithyroglobulin antibodies (ATGAb) and thyroid peroxidase antibodies (TPOAb). Also, complete blood picture, ESR, RF, ANA, CRP and LE cells were done. This study revealed that thyroid disorders were significantly increased in SLE patients (50%) when compared to RA (15%) (P<0.05). In SLE group, 20% had euthyroid sick syndrome, 20% had hypothyroidism (10% subclinical and 10% biochemical), and 10% had hyperthyroidism (5% subclinical and 5% biochemical). However, in RA, 10% had hypothyroidism (subclinical) and 5% had subclinical hyperthyroidism. TPOAb was found in 15% of SLE and 5% of RA patients and 10% of controls, but the titres were higher in SLE and RA patients. Also, ATGAb was found in 5% of SLE, 30% of RA patients and 10% of controls, but the titres were higher in SLE and RA patients. It is concluded that thyroid abnormalities are more implicated with euthyroid sick syndrome and hypothyroidism (subclinical and overt) than hyperthyroidism in SLE patients. SLE and RA were associated with antithyroid antibodies (TPOAb in SLE and ATGAb in RA). Performance of thyroid function tests in patients with SLE, in particular and RA as a part of the biochemical and immunological profiles, may help in early detection of associated thyroid disorders.
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PMID:Thyroid disorders and autoantibodies in systemic lupus erythematosus and rheumatoid arthritis patients. 1673 20

We examined the prevalence of thyroid dysfunction and the production of anti-thyroid antibodies (ATA) in patients with systemic lupus erythematosus (SLE) and assessed the association between ATA production and SLE disease activity status. Seventy-seven patients who met the American College of Rheumatology classification criteria for SLE participated in the study. Fifty-two individuals served as a control group. Demographic, clinical information and SLE disease activity (SLEDAI) status were collected from all patients. The sera of all participants were tested for free thyroxine (FT4), thyroid-stimulating hormone (TSH), anti-thyroglobulin (ATg) and anti-thyroid peroxidase (TPO). A SLEDAI score of > or =6 was considered clinically significant. The results of the thyroid function tests and ATA were compared between the study group and the control group. ATA levels were compared between the patients with a SLEDAI score of > or =6 to those with a SLEDAI score of <6. Hypothyroidism was detected in 11.6% of SLE patients compared to 1.9% in the control group. None of the patients or controls had evidence of hyperthyroidism. No statistically significant difference was observed in the levels of ATg or TPO between the study group and the control group. No correlation was found between ATA levels and the degree of the disease activity. Among the different variables tested in this study, hypothyroidism was the only significant abnormal finding in SLE patients. No association was found between the SLEDAI score and the prevalence of ATA production. Larger controlled, longitudinal studies are necessary to confirm these findings and elucidate the role played by ATA in the pathogenesis of thyroid dysfunction in SLE patients.
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PMID:Thyroid dysfunction in patients with systemic lupus erythematosus (SLE): relation to disease activity. 1737 71

Data on thyroid disease in Arabs with lupus is scarce. We conducted a cross-sectional and retrospective case-control study to report the prevalence of thyroid diseases in 110 Arabs with lupus who attended our Rheumatology Clinic between January 2002 and January 2007, and to delineate the clinical and immunological features of Arabs lupus patients with thyroid diseases. We found hypothyroidism in 15 (13.7%) patients. Overall, 25.6% had elevated thyroid peroxidase antibodies, 14.6% had elevated anti-thyroglobulin antibodies, and 13.7% were positive for both antibodies. Lupus patients with hypothyroidism had a significantly higher frequency of polyarthritis (OR = 9.3, CI: 2.0-41.7, P < 0.001), cutaneous manifestations (OR = 5.6, CI: 2.4-14.3, P < 0.0001), positive anti-thyroglobulin antibodies (OR = 19.9, CI: 8.38-47.4, P < 0.0001), and thyroid peroxidase antibodies (OR = 12.3, CI: 6.27-24.1, P < 0.0001) than lupus patients with normal thyroid function. Furthermore, neuropsychiatric (OR = 0.36, CI: 0.14-0.93, P < 0.05) and hematological (OR = 0.52, CI: 0.29-0.91, P < 0.05) manifestations were significantly lower in patients with hypothyroidism than in euthyroid patients. Surprisingly, the prevalence of anticardiolipin antibody immunoglobulin G (aCL IgG) (OR = 0.34, CI: 0.13-0.86, P < 0.05), lupus anticoagulant (OR = 0.02, CI: 0.001-0.35, P < 0.0001), and anticardiolipin syndrome (OR = 0.02, CI: 0.001-0.43, P < 0.0001) were significantly lower in lupus patients with hypothyroidism than in lupus patients with normal thyroid function. In conclusion, the prevalence of hypothyroidism in Arabs with lupus is comparable to that reported in the literature. Arab lupus patients with hypothyroidism have distinctive clinical and immunological features that differentiate them from euthyroid patients.
Lupus 2008 Mar
PMID:Hypothyroidism determines the clinical and immunological manifestations of Arabs with lupus. 1837 63

Autoantibodies against complement C1q (anti-C1q) have been well described in patients with systemic lupus erythematosus, where they correlate with the occurrence of severe lupus nephritis. However, data on anti-C1q in organ-specific autoimmune diseases are scarce. In order to determine the prevalence of anti-C1q in patients with autoimmune thyroid disorders (AITD) and a possible association with thyroid function, we measured prospectively anti-C1q in 23 patients with Graves' disease (GD) and 52 patients with Hashimoto's thyroiditis (HT). Anti-C1q levels were correlated with parameters of thyroid function and autoantibodies against thyroperoxidase, thyroglobulin and thyroid stimulating hormone (TSH) receptor. Twenty-one patients with multi-nodular goitre and 72 normal blood donors served as controls. We found elevated concentrations of anti-C1q more frequently in patients with AITD than in controls: seven of 23 (30%) patients with GD and 11 of 52 (21%) patients with HT, compared with one of 21 (5%) patients with multi-nodular goitre and six of 72 (8%) normal controls. Anti-C1q levels did not correlate with thyroid autoantibodies. However, in GD absolute levels of anti-C1q correlated negatively with TSH and positively with free thyroxine (FT4) and triiodothyronine (FT3). In contrast, in HT, anti-C1q correlated positively with TSH levels. No correlation between TSH and thyroid autoantibodies was found. In conclusion, we found an increased prevalence of anti-C1q in patients with AITD and their levels correlated with the thyroid function in both GD and HT. This correlation seems to be independent of thyroid autoantibodies. Therefore, anti-C1q might point to a pathogenic mechanism involved in the development of AITD that is independent of classical thyroid autoantibodies.
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PMID:Autoantibodies against complement C1q correlate with the thyroid function in patients with autoimmune thyroid disease. 1850 35

The aim of this study was to evaluate the frequency of thyroid dysfunction and thyroid antibodies in patients with juvenile onset Systemic Lupus Erythematosus (JOSLE) and its association with clinical and immunological features. Seventy-seven patients with JOSLE, 64 females, median age 19 years, were consecutively enrolled from March to December 2007. Clinical data related to thyroid dysfunction and lupus were obtained by chart review and patient interview. Serum levels of TSH, free T4, anti-thyroglobulin (TgAb), anti-thyroperoxidase (TPOAb), TRAb and lupus related autoantibodies were analyzed by standard techniques. Nine patients were diagnosed as hypothyroidism and 4 hyperthyroidism. 28% JOSLE patients had moderate/high titer of thyroid antibodies: 23% TgAb, 2.6% TPOAb and 3.9% TRAb. JOSLE patients with positive thyroid autoantibodies had higher frequency of anti-U1RNP antibodies than patients without these antibodies (40.9 vs. 14.5%, OR:0.25, CI:0.08-0.76, p = 0.017). Furthermore, renal/neurological/hematological involvement was less frequently observed in patients with hypothyroidism (55.6 vs. 87.5%, OR:0.18, CI:0.04-0.81, p = 0.035) and with thyroid antibodies (68.4 vs. 90.9%, OR:0.22, CI:0.06-0.82, p = 0.027) than in patients without these alterations. No association with PTPN22 polymorphism was found. In conclusion, JOSLE patients have high prevalence of subclinical hypothyroidism. The novel association of anti-thyroid antibodies with anti-U1RNP antibodies in JOSLE seems to identify a subgroup of patients with less life-threatening organ involvement.
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PMID:Juvenile onset Systemic Lupus Erythematosus thyroid dysfunction: a subgroup with mild disease? 1941 39


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