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

The aim of this work was to characterise the eye muscle antigens reacting with autoantibodies from Graves ophthalmopathy patients to elucidate the function of these antibodies. As estimated by ELISA test antibodies of IgG class reacting with porcine microsomal membranes are present in about 25% of patients while of IgM class in about 15% of patients with Graves ophthalmopathy. Their presence do not correlate with ophthalmopathy index, neither they have relation to treatment. Anti eye muscle antibodies were present at some stages of the disease in three patients who develop ophthalmopathy, from the group of 26 patients treated during one year for hyperthyroidism. However, sporadically these antibodies were found also in about 20% of patients with Hashimoto disease, Lupus erythematosus or Scleroderma. Some of them cross react with antigens of skeletal muscle and liver. Eye muscle antigens reacting with patients antibodies are localised in plasma membranes and in membranes of smooth reticulum. Affinity purification of solubilised porcine eye muscle membrane proteins on a column with immunoglobulins from pooled serum of patients resulted in 23 fold purification of the antigen. The sensitivity of ELISA was not significantly increased by the use of affinity purified antigen, however some of previously negative ophthalmopathy sera gave positive reaction. Porcine eye muscle membrane proteins were separated by SDS PAGE and transferred to nitrocellulose. The reactions of electroblotted proteins with sera from patients with Graves ophthalmopathy and also sera from healthy controls shown very complex pattern. There was not a single antigen or antigens reacting only with antibodies present in sera of ophthalmopathy patients and not in controls. Patients sera reacted more often than control sera with an antigen of about 40 kDa. The reaction of sera from some patients with proteins about 100, 70 and 65 kDa were stronger than between these proteins and control sera. No changes in the pattern of reaction between antibodies and eye muscle antigens were noticed in serum of the same Graves' patient with or without ophthalmopathy during one year follow up and treatment, regardless of clinical course of the disease. When human eye muscle membrane fractions from tissue obtained during strabismus repair or at autopsy was used for immunoblotting, smaller number of proteins reacted with autoantibodies. Again there was no single antigen or antigens reacting with antibodies from sera of all Graves ophthalmopathy patients. Sera of some patients reacted with antigens about 50 kDa, not recognized by controls. The results of present study show, that the anti eye muscle antibodies are present in some of Graves ophthalmopathy patients.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Muscle antigens recognized with autoantibodies in patients with Graves' ophthalmopathy]. 134 58

Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment.
 ...
PMID:The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation. 185 15

Evidence suggests that N-oxidized metabolites of procainamide may be responsible for the development of lupus-like symptoms associated with procainamide therapy. The human hepatic microsomal metabolism of procainamide has been previously reported to result in formation of the N-hydroxylamine derivative of procainamide (procainamide hydroxylamine [PAHA]). The objective of this study was to examine the effects of PAHA on human lymphocytes and adherent cells (monocytes and macrophages). When incubated with lymphocytes in whole blood, PAHA enhanced the response to mitogen and immunoglobulin secretion at lower concentrations (less than or equal to 4 mumol/L) but suppressed these functions at higher concentrations. The cytotoxic effects were nonselective for T lymphocytes and B lymphocytes and appeared to involve an interaction between PAHA and hemoglobin. When erythrocytes were removed or when hemoglobin was converted to carboxyhemoglobin, the suppressive effects of PAHA on lymphocytes were reduced. PAHA stimulated interleukin-1 production by adherent cells at 25 mumol/L but had no effect at lower concentrations. Superoxide anion release was unaffected by PAHA in "resting" adherent cells. Pretreatment with PAHA (2 mumol/L) diminished superoxide release in response to stimulation by phorbol myristate acetate (PMA) or latex bead phagocytosis but augmented superoxide release when coincubated with PMA or latex. These observations indicate that PAHA produces complex, concentration-dependent interactions with human immunoregulatory cells, and they suggest that the effects of PAHA on lymphocyte function may result from the further oxidation of PAHA by hemoglobin, perhaps to the nitroso form.
 ...
PMID:Immunomodulatory effects of procainamide metabolites: their implications in drug-related lupus. 253 20

We have demonstrated previously that procainamide is metabolized to a hydroxylamine. The reactivities of this hydroxylamine and of the closely related nitroso derivative toward biological molecules were investigated with the objective of exploring possible mechanisms of procainamide-induced lupus. The hydroxylamine of procainamide was found to bind covalently to microsomal protein to a much greater degree than did procainamide and, in contrast to procainamide, it did not require metabolic activation. However, the hydroxylamine is readily converted nonenzymatically to the nitroso derivative, and reducing agents such as ascorbate and NADPH, which reduce the nitroso derivative to the hydroxylamine, blocked covalent binding. This suggests that the nitroso derivative is the reactive species for covalent binding. Furthermore, glutathione had been shown previously to block covalent binding of procainamide metabolites, and the nitroso derivative, but not the hydroxylamine, reacted rapidly with glutathione forming a sulfinamide derivative. The covalent binding of the nitroso derivative to microsomal protein appears to involve sulfydryl groups, because it, like the glutathione adduct, was readily cleaved by mild acid. In contrast, the nature of the covalent binding to albumin and histone protein appears different from that to microsomal protein in that most of the binding was stable to mild acid. The reactivity toward DNA was much less than that to protein. The observation that both the reactivity of nitrosoprocainamide and the specificity of antinuclear antibodies in procainamide-induced lupus are to histone protein rather than the DNA supports the hypothesis that this reactive metabolite plays a role in the etiology of procainamide-induced lupus.
 ...
PMID:Reactivity and possible significance of hydroxylamine and nitroso metabolites of procainamide. 396 43

We have previously demonstrated that procainamide is oxidized to a reactive metabolite. We speculated that this reactive metabolite might be a hydroxylamine and further that it might be responsible for the syndrome of procainamide-induced lupus. We now report that procainamide is metabolized to a hydroxylamine by rat and human hepatic microsomes. The extent of this metabolic oxidation was quantitated by HPLC after conversion of the hydroxylamine to the more stable nitro derivative of procainamide. Formation of the hydroxylamine required NADPH, active microsomes, and oxygen and was inhibited by carbon monoxide, SKF 525-A, and cimetidine. Formation of the hydroxylamine was also studied as a function of time, microsomal protein concentration, and procainamide concentration.
 ...
PMID:Metabolism of procainamide to a hydroxylamine by rat and human hepatic microsomes. 614 17

The principal metabolic pathway of procainamide leads to formation of the less toxic N-acetyl-procainamide and the rapid acetylator phenotype is associated with a lower incidence of procainamide-induced lupus. Another metabolic pathway forms a reactive metabolite which causes revertants in the Ames test and covalently binds to microsomal protein. A study of the metabolism of procainamide revealed three metabolites that have not been previously described. A comparison of the metabolites of N-acetylprocainamide with those of procainamide suggests possibilities for the identity of the reactive metabolite. The hypotheses to be discussed explore the relationships between the formation of a reactive metabolite and the induction of lupus.
 ...
PMID:The implications of procainamide metabolism to its induction of lupus. 616 52

The presence of circulating antibodies directed against a cytoskeletal element, microtubules, in patients with autoimmune thyroid disorders, has been studied using pure brain tubulin as antigen. Immune complexes were immunoprecipitated using a goat anti-human immunoglobulin antibody. Twenty sera among 48 (41%) from patients with Graves' disease and nine sera among 16 (56%) from patients with Hashimoto's thyroiditis had increased levels of anti-tubulin antibodies as compared to that of 26 sera from control subjects. Only one serum among 11 from patients with toxic adenoma was positive. Very similar results were obtained using protein A adsorbent to collect immune complexes. Specificity of the tubulin binding activity was ascertained by dilution of the sera and displacement of tracer tubulin by unlabelled pure tubulin from rat or human brain. Anti-tubulin antibody titres were variable; one serum was positive at dilution higher than 1:15,000, a titre similar to those obtained in animals experimentally immunized against tubulin. Binding of labelled and unlabelled tubulin to immunoglobulins from positive sera was strictly competitive. The apparent affinity constant for the binding of tubulin to human anti-tubulin autoantibodies determined on four sera was 0.2-0.6 X 10(9)/M. There was no significant association between anti-tubulin antibodies and anti-microsomal antibodies or anti-thyroglobulin antibodies or thyroid stimulating antibodies. In contrast, only five to six per cent of sera from patients with other autoimmune diseases: lupus erythematosis or pernicious anaemia, had increased levels of anti-tubulin antibodies. In conclusion, tubulin represents a new autoantigen which is expressed rather specifically in autoimmune thyroid disorders and probably independently from the classical thyroid antigens.
 ...
PMID:Anti-tubulin antibodies in autoimmune thyroid disorders. 668 44

Thirty four sera from: 12 patients with Systemic Lupus Erythematosus (SLE), 9 with Subacute Cutaneous Lupus Erythematosus (SCLE) and 13 with Discoid Lupus Erythematosus (DLE) (disseminatus 3, localised 10) were tested for the presence of: (a) anti-thyroglobulin and anti-microsomal autoantibodies (b) anti-Sm/RNP, anti-doublestranded. DNA (anti-ds. DNA), anti-single-Stranded. DNA (anti-ss. DNA), anti-cardiolipin (anti-Cl), anti-SSA, anti-SSB, Antinuclear Antibodies (ANA). T3, T4, TSH levels were also determined. Five patients with SLE (41.6%), 4 with SCLE (44.4%), and 2 with DLE (15.3%) had thyroid autoantibodies and only three of the 41 controls (7.3%). Five patients (14.7%), especially from SLE and SCLE groups, had biochemical hypothyroidism whereas only one had hyperthyroidism. Statistical evaluation for the possible coexistence of thyroid autoantibodies with a panel of lupus characteristic autoantibodies, revealed highly significant correlations with anti-Sm/RNP, IgG (p = 0.003) and anti-ds. DNA, IgM (p = 0.012). It may be concluded, that not only SLE but also SCLE predisposes to autoimmune thyroid disease and the prevalence of the latter is related to a great extent to the subset of the LE spectrum. From these results and from the inhibition experiments, it seems that some of the specific mono- or polyclonal autoantibodies may be multiple organ reactive.
 ...
PMID:Thyroid autoantibodies in the subsets of lupus erythematosus: correlation with other autoantibodies and thyroid function. 750 37

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

Reproductive life table analysis indicates that the majority of reproductive failures result from post fertilization failures, whether before or after implantation. It is important to have a set of tests to clarify the diagnosis of the reproductive failure so that appropriate therapy can be instituted. To determine the frequency of abnormal immunologic tests among women experiencing reproductive failure, 108 patients were evaluated for the presence of antiphospholipid antibodies (APA); lupus anticoagulant (LA); thyroid-thyroglobulin and microsomal antibodies (TGT); embryotoxic factor (ETA); and systemic CD56+/CD16- cells. The frequency of abnormal results obtained from testing for APA, LA, TGT, ETA, and CD56+/CD16- cells among 108 patients with diagnoses of recurrent pregnancy loss (RPL)(n = 45), unexplained infertility (n = 45) including IVF failure (n = 10), endometriosis (n = 10), premature ovarian failure (n = 5), and polycystic ovaries (n = 3) were compared with 15 normal controls. Seventy of one hundred eight (65%) women experiencing reproductive failure had at least one positive test, compared to 1 of 15 (7%) controls (P = 0.0001). Presence of phospholipid antibodies was the most frequently abnormal result followed by elevated CD56+/CD 16 cells. The prevalence of a particular abnormal test varied among the diagnoses. The most frequent abnormal test among women with RPL was an increased percentage of CD56+/CD16- cells (40%), followed by APAs (29%), TGT (9%), and ETA (7%). The most frequent abnormal result among women with unexplained infertility was the presence of APAs (42%), followed by CD56+/CD16- cells (16%), ETA (16%), and TGT (9%). APA, CD56+/CD16- cells, ETA, and TGT are useful tools to assist in the diagnosis of reproductive failure.
 ...
PMID:Laboratory evaluation of women experiencing reproductive failure. 873 63


1 2 Next >>