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)

MRL-lpr/lpr mice manifest a systemic lupus-like autoimmune disease. As part of this syndrome, the mice spontaneously develop autoimmune thyroiditis, which is morphologically and biochemically similar to human autoimmune thyroiditis. In this study we investigated whether thyroid tissue obtained from sites of chronic inflammation had altered gap junctional communication. Fresh tissue sections revealed that thyroid from the nondiseased mice (MRL-(+)/+) had connexins (Cx) localized to the plasma membrane at points of thyroid cell-cell contact. In contrast, the Cx in diseased mouse (MRL-lpr/lpr) thyroid tissue were not localized to the plasma membrane, and the fluorescent intensity was reduced for Cx43 and Cx26. Northern analysis confirmed that murine thyroid tissue expressed messenger RNA for these Cx. However, the diseased tissue expressed lower levels of Cx32 and Cx26 messenger RNA. The infiltrating cells and their biologically active products present in the diseased thyroid tissue may mediate the reduced Cx expression and aberrant gap junctional assembly. We established primary thyrocyte cultures to determine whether these differences persisted when the inflammatory factors were removed. The nondiseased thyroid cells were communication competent, with fluorescent dye transfer proceeding from the injected cell to primary contacts (95%) and to second and third order neighboring cells in 75% of the trials. Thyroid cells from the diseased mice were communication incompetent, in that 80% of microinjections failed to result in dye transfer to cells in direct contact. Immunocytochemistry indicated that the functional coupling in the normal mouse thyroid cells was associated with Cx43 located in the plasma membrane as assembled gap junctional plaques. The communication-deficient diseased thyroid cells had internalized Cx43 predominantly localized to perinuclear regions of the cells. Collectively, these data document altered Cx-protein distribution in the autoimmune diseased thyroid. The diseased thyroid tissue was devoid of plasma membrane identifiable gap junctions and deficient in intercellular communication. Culturing removed the inflammatory mediators; however, the disease cells retained their communication incompetence. These results suggest that if this deficiency was initiated by components of the inflammation process, then protracted changes must have occurred so that the continued presence of these factors was no longer required to sustain this difference.
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PMID:Reduced cell-cell communication in a spontaneous murine model of autoimmune thyroid disease. 762

Thyroid microsomal antibodies (Ms-Ab) are recently proved to be directed to thyroid peroxidase (TPO). The aim of this study was to investigate whether the sera of patients with systemic lupus erythematosus (SLE) contain anti-TPO antibodies (TPO-Ab) and whether these antibodies influence enzyme activity. Sera from patient with Hashimoto's thyroiditis was also studied. Serum samples were obtained from 37 patients with SLE, 20 patients with Hashimoto's thyroiditis and 20 healthy subjects. TPO-Ab were detected by immunoprecipitation using crude microsomal preparations or enzyme-linked immunoabsorbent assay (ELISA) with recombinant TPO. Positive TPO-Ab by ELISA were found in 11 (61%) of 18 patients with lupus whose serum contained Ms-Ab. Low levels of TPO-Ab also were found in three (16%) of 19 lupus sera that did not contain Ms-Ab. All patients with Hashimoto's thyroiditis had high levels of TPO-Ab in serum. When measured by ELISA, TPO-Ab were highly correlated with the results of a TPO immunoprecipitation assay and with the titers of Ms-Ab in patients with lupus (r = 0.83, n = 18, P < 0.01; r = 0.63, n = 18, P < 0.01) and in Hashimoto's thyroiditis (r = 0.89, n = 20, P < 0.01; r = 0.75, n = 20, P < 0.01). When evaluating the direct influence of TPO-Ab on the activity of TPO, we found no significant inhibition of enzymatic activity in both guaiacol and iodide assays by lupus sera in contrast with sera from Hashimoto's thyroiditis.(ABSTRACT TRUNCATED AT 250 WORDS)
Lupus 1995 Aug
PMID:Thyroid peroxidase autoantibodies and their effects on enzyme activity in patients with systemic lupus erythematosus. 852 24

Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.
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PMID:Adverse effects of thyroid hormone preparations and antithyroid drugs. 886 63

The aim of the present study was to identify the risk factors for ovarian failure in patients with systemic lupus erythematosus. Seventy-one women aged 17 to 45 years with systemic lupus erythematosus were studied. Patients were interviewed and their medical records reviewed. Demographic characteristics, clinical and serologic profiles, and menstrual and obstetric histories were recorded. Disease activity was measured by the systemic lupus erythematosus disease activity index. Serum FSH, LH, estradiol, progesterone, TSH, prolactin, and antimicrosomal and antithyroglobulin antibodies were measured. Patients who developed ovarian failure were compared to those who did not. Ovarian failure occurred in 11 patients (15.5%) and nine had premature menopause (11.3%). Cyclophosphamide administration and older patient age were found to be associated with ovarian failure. The cumulative cyclophosphamide dose was significantly higher in patients with ovarian failure than in those without this condition (18.9 vs 9.1 g; P = 0.04). The relative risk for ovarian failure in patients with cumulative cyclophosphamide dose higher than 10 g was 3.2. TSH levels were high in 100% of patients with ovarian failure who had received pulse cyclophosphamide. Ovarian failure, and premature menopause in particular, is common in patients with systemic lupus erythematosus, with the most important risk factors being cyclophosphamide dose and age. Thyroid problems may be another risk factor for ovarian failure in patients with lupus.
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PMID:Risk factors for ovarian failure in patients with systemic lupus erythematosus. 1171 9

To determine the heritable component of Graves' disease (GD) more precisely, a disease survey questionnaire completed by 13,726 California-born twin pairs over the age of 37 years was used as the foundation of this study. On the basis of this survey, each member of pairs reporting a past diagnosis of GD was then sought for an extensive telephone interview to seek diagnostic confirmation. Successful diagnostic evaluation occurred in 108 cases, of which 99 affected twin pairs form the basis of this report. The results indicate that the estimated pairwise concordance for is 17% in monozygotic (MZ) twins, and 1.9% in dizygotic (DZ) twins, which are in close agreement with a recent report from a Danish twin population. Moreover, the reported 3.9% occurrence of GD found in the first-degree relatives of affected twin pairs supports these findings. In contrast, only 0.45% of all twins, 0.27% of the spouses of twins, and approximately 0.16% of the first-degree relatives of unaffected twins were reported to have GD. Additionally, among the unaffected MZ twins of patients with GD, 17% reported having chronic thyroiditis and 10% other nonthyroid autoimmune conditions such as lupus erythematosus, pernicious anemia, or idiopathic thrombocytopenic purpura. Thus, a genetic predisposition appears to be shared for both thyroid and some nonthyroid autoimmune diseases. While it seems that GD is a strongly and nonspecifically heritable condition, the relatively low level of twin concordance indicates that this disease likely requires a nonheritable etiologic determinant(s) as well.
Thyroid 2002 Aug
PMID:Further evidence for a strong genetic influence on the development of autoimmune thyroid disease: the California twin study. 1222 32

Mitral valve prolapse (MVP) has been reported to be associated with systemic lupus erythematosus (SLE). The aim of the present study was to determine the prevalence of MVP in SLE patients, assess its clinical significance and examine the possible association of this entity with other autoimmune indices. Eighty-seven consecutive SLE patients attending the rheumatology clinic and 73 normal control subjects were examined by M-mode, two-dimensional color-Doppler echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. MVP was detected in 19/87 patients with SLE and in four of the healthy controls(P = 0.0057). SLE patients with MVP were younger (33.6 +/- 12.4 years) than those without MVP (41. +/- 12.9, P = 0.04) and with shorter duration of the disease (P = 0.03). We found a statistically higher prevalence of anticardiolipin antibodies (aCL) in SLE patients with prolapse (11/19) compared with SLE patients without prolapse (15/68, P = 0.04). This association was independent of age. The aCL-lgG levels were significantly higher in SLE patients with MVP (32.37 +/- 43.26) compared with SLE patients without MVP (22.24 +/- 29.95, P = 0.04). Thyroid autoantibodies tended to be more common in S LE patients with MVP. Th e prevalence of MVP is increased in SLE patients. The presence of aCL and of organ-specific autoantibodies in SLE patients with MVP might indicate the autoimmune origin of MVP. The possibility that SLE patients with MVP may be predisposed to further autoimmune diseases should be considered.
Lupus 2003
PMID:Mitral valve prolapse in systemic lupus erythematosus patients: clinical and immunological aspects. 1272 55

A young male presented with oral ulceration for two years; swelling face and feet of seven days duration; diffuse goiter without signs of thyroid disease; normocytic normochromic anemia, thrombocytopenia, deranged renal functions, albuminuria of 2.5 g/24h with active urinary sediment. ANA and anti-ds DNA were positive, sonography of abdomen suggested medical renal disease. Testing for HIV, HBV, VDRL, CRP, rheumatoid factor, p-ANCA and c-ANCA were negative. Thyroid hormone assays were normal. Kidney biopsy done to stage lupus nephritis did not show any evidence of lupus involvement but staining for SAA amyloid was positive. Subsequent biopsies from the liver and rectum also stained positive for amyloid. Diagnosis of "Systemic lupus erythematosus with renal and systemic secondary amyloidosis with euthyroid diffuse goiter" was made. The case is being reported and discussed because of the interesting and rare association between amyloidosis and systemic lupus erythematosus.
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PMID:Renal and systemic amyloidosis in systemic lupus erythematosus. 1291 Nov 74

A 35-year-old Asian male, treated for hyperthyroidism, systemic lupus erythematosis, and uremia presented with low serum total thyroxine (T4) and normal serum thyrotropin (TSH) levels. He had been receiving prednisone and methimazole for 15 weeks. Free T4 measured by direct equilibrium dialysis was in the hypothyroid range (0.3 ng/dL; normal, 0.8-2.7). Two possibilities were considered: (1) a weakly bound dialyzable inhibitor in uremic serum that interfered with this serum free T4 determination or (2) hypothyroidism with persistent TSH suppression because of prior hyperthyroidism. To determine whether a weakly bound inhibitor was involved, the patient's serum was serially diluted using two diluents: (1) an ultrafiltrate of the patient's serum, which would contain any unbound inhibitor, as well as free T4 and (2) an inert diluent. Free T4 measurements were similar with both, providing evidence against the presence of a dialyzable and ultrafilterable inhibitor. In conclusion, this patient was hypothyroid because of antithyroid drug administration, associated with prolonged central TSH suppression from preexisting hyperthyroidism. Discontinuation of methimazole resulted in normalization of serum total T4 and TSH values. Thus, paired, serial serum dilutions, using two different diluents, provided evidence for differentiation of appropriately low free T4 measurements (because of hypothyroidism), from spuriously low free T4 measurements (because of an interfering inhibitor).
Thyroid 2004 May
PMID:Assessing thyroid hormone status in a patient with thyroid disease and renal failure: from theory to practice. 1518 19

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.
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PMID:Klinefelter's syndrome presenting with leg ulcers. 1536 65

In face of numerous benefits induced by therapy based on interferon (IFN) associated with ribavirin for the treatment of chronic hepatitis C, there is an increasing concern regarding its tolerance, which can, in some cases, reduce the quality of life as well as compliance of patients. Among the less common side effects, there are the autoimmune ones which can be globally divided into appearance or increase in titres of auto-antibodies and/or manifestation of overt autoimmune pathologies. Whereas the former may concern more than 50% of treated subjects, the latter is reported in only 1-2% of patients under therapy. Thyroid dysfunction represents the well-studied autoimmune disorder. The presence of pre-existing anti-thyroid antibodies and being of female sex, constitute relevant risk factors for the development of a disease involving this gland. Often the treatment of thyropathy must be continuous in spite of IFN discontinuation because the disturbance usually does not abate with stopping antiviral therapy. Some observations have pointed out to the fact that IFN can lead to the development of insulin-dependent diabetes mellitus. Sometimes, during, as well as after IFN treatment, the appearance of anti-islet cell antibodies has been shown, but its interrelationship with the development of disease is uncertain. While being treated with IFN for chronic hepatitis C, the finding of non-organ specific antibodies at baseline can increase the likelihood of the development of autoimmune hepatitis. However, their presence does not constitute an absolute contraindication to the treatment, except in case of high titre. Other disorders, such as a lupus erythematosus-like syndrome, haemolytic anaemia, and immune-mediated thrombocytopenia have been reported. In conclusion, although the presence of auto-antibodies is considered to be an epiphenomenon without pathogenic significance in most patients suffering from chronic hepatitis C, it poses a problem when they need to be treated with IFN. This antiviral drug can induce or exacerbate a multitude of autoimmune-related disorders, however, clinically overt immune-mediated diseases are rare and affect a subset of subjects who have an underlying autoimmune diathesis.
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PMID:Autoimmune manifestations during interferon therapy in patients with chronic hepatitis C: the hepatologist's view. 1575 46


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