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)

Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with clinically proven vasculitis have been described as reacting with proteins present in the granules of human neutrophils. We have studied sera from 59 ANCA positive patients to further characterize the antibody response. In addition to the antigens previously identified in the vasculitic syndromes (myeloperoxidase and serine proteinase 3) the majority of these sera contained antibodies that reacted with a cytosolic extract of neutrophils on Western blots. Nearly 40% of these sera had antibodies directed against a cytosolic protein(s) of molecular mass 48 kD. This protein was purified from neutrophil cytosol by ammonium sulphate fractionation, anion exchange and reverse phase chromatography. Amino acid sequence analysis of a proteolytic fragment of this protein identified it as alpha enolase. The anti-enolase antibodies only recognized the alpha isoform and were present in sera giving either a pANCA or cANCA staining pattern by indirect immunofluorescence. Antibodies to alpha enolase were also found in sera from patients with systemic lupus erythematosus, particularly those with renal disease. We conclude that the antibody response in ANCA positive vasculitis is not restricted to neutrophil granule proteins.
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PMID:Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis. 845 67

The anti-hypertensive agent hydralazine can cause a lupus-like syndrome characterized by serosal inflammation, arthralgias and rashes. The kidneys however are usually spared. The condition is characterized by circulating immune complexes and antinuclear antibodies, whilst antibodies against double-stranded DNA are rare. Hydralazine can also cause a systemic vasculitis with a pauci-immune rapidly progressive glomerulonephritis, which is associated with autoantibodies directed against components of the neutrophil cytoplasm. In this study, ten patients with hydralazine-induced vasculitis had antibodies with specificities for both myeloperoxidase and lactoferrin. We suggest that this particular pattern of autoantibodies, together with antibodies with reactivity against nuclear components including double-stranded DNA, are characteristic findings in hydralazine-induced vasculitis. In addition, renal involvement appears to be more common in this group of patients with vasculitis than in those with the lupus-like syndrome.
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PMID:Antigen specificity in hydralazine associated ANCA positive systemic vasculitis. 854 62

Anti-neutrophil cytoplasmic antibodies (ANCA) are a system of autoantibodies which are strongly associated with the primary systemic vasculitides (PSV). cANCA, as detected by indirect immunofluorescence, are mostly reactive to proteinase 3 (PR3) and bear high sensitivity and specificity for Wegener's granulomatosis. pANCA have varied subspecificities and clinical associations. The most important subspecificity of pANCA is anti-myeloperoxidase (MPO), which is strongly associated with microscopic polyaniitis and pauci-immune crescentic glomerulonephritis. pANCA also occur at low to moderate frequency in other PSV, collagen vascular disease, inflammatory bowel disease and autoimmune liver disease. In systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), pANCA of varied subspecificity have been found, including anti-MPO at low rate and low titer, while cANCA and anti-PR3 were generally absent. Consequently, anti-PR3 (PR3-ANCA) and anti-MPO (MPO-ANCA) at moderate and high titer are distinguishing features of the PSV and, in an appropriate clinical setting, argue strongly against the presence of SLE or RA. Since no significant clinical association has been found for other pANCA subspecificities, cANCA, PR3-ANCA and MPO-ANCA remain the critical elements of ANCA testing in the clinical diagnosis of generalized autoimmune diseases.
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PMID:Anti-neutrophil cytoplasmic antibodies in generalized autoimmune diseases. 862 87

We determined the occurrence of antineutrophil cytoplasmic antibodies (ANCAs) and their specificities in 77 rheumatoid arthritis (RA) patients and compared them with 25 patients with psoriatic arthritis (Pso), 19 with drug-induced lupus erythematosus (DI-LE) and 11 with systemic lupus erythematosus (SLE). Thirty-two percent of RA patients had positive indirect immunofluorescence (IIF) stains (P or atypical ANCA). Twenty-nine per cent of patients with rheumatoid vasculitis (RAV), 48% with long-standing RA (LSRA) and 20% with early RA (Ely RA) had positive ANCAs compared with 4% of Pso patients, 47% of DI-LE patients and 45% of SLE patients. Western blotting (with polymorphonuclear cell extracts or alpha-granules) and alpha-granule enzyme-linked immunosorbent assay (ELISA) yielded variable results and proved unhelpful for characterizing the specificities of ANCAs. ELISAs based on commercial purified lactoferrin (LF), myeloperoxidase (MPO), human elastase (HLE) and cathepsin G (CG) showed that anti-HLE antibody was the most prevalent (14%) antibody in RA, followed by anti-MPO antibody and anti-LF antibody (10% each). Statistical analysis of antibody prevalence by clinical presentation showed that LSRA patients were more likely to have anti-HLE antibody and that DI-LE patients were more likely to have anti-CG antibody compared with the other patient groups. In lupus patients serial ELISA titration of ANCAs (LF and MPO) was found to be reliable for predicting the outcome. The overall incidence of ANCAs in RA patients was 33% by IIF.
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PMID:Antineutrophil cytoplasmic antibodies in rheumatoid arthritis patients. 862 21

Previously, we have shown that it is possible to induce, in naive mice, systemic autoimmune diseases (e.g., antiphospholipid syndrome and systemic lupus erythematosus) by idiotypic manipulation. In the present study we expanded our experience to examine whether idiotypic manipulation could be utilized to induce organ-specific autoantibodies and a disease mediated by cellular mechanisms, namely, experimental autoimmune thyroiditis. Fifteen BALB/c mice were immunized with a monoclonal mouse anti-human thyroglobulin (hTg) antibody; controls were immunized with an irrelevant mouse IgG. The mice immunized with anti-hTg antibody developed, 6 weeks after immunization, autoantibodies to human thyroglobulin, but not to dsDNA, cardiolipin, or myeloperoxidase. The presence of specific autoantibodies was associated with low production of thyroid hormones, and during a follow-up of 20 weeks the mice did not develop characteristic histological signs of thyroiditis. We conclude that idiotypic manipulation can induce anti-thyroglobulin autoantibodies.
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PMID:Induction of thyroid autoantibodies in naive mice by idiotypic manipulation. 862 60

Reactive metabolites are believed to be responsible for many types of toxicity, including idiosyncratic drug reactions. Bone marrow is a frequent target of idiosyncratic reactions, and, since these reactions have characteristics that suggest involvement of the immune system, the formation of reactive metabolites by leucocytes could also play a role in the aetiology of idiosyncratic drug reactions. The major oxidation system in neutrophils and monocytes is a combination of NADPH oxidase and myeloperoxidase. This system oxidizes primary arylamines, such as sulphonamides, to reactive metabolites and these drugs are also associated with a high incidence of agranulocytosis, generalized idiosyncratic reactions and/ or drug-induced lupus. Clozapine is oxidized by this system to a relatively stable nitrenium ion; clozapine is also associated with a high incidence of agranulocytosis. Arylamines that have an oxygen or nitrogen in the para position, such as amodiaquine, vesnarinone and 5-aminosalicylic acid, are oxidized to quinone-like reactive intermediates. Aminopyrine is oxidized to a very reactive dication. Such reactive metabolites could also inhibit neutrophil function and mediate some of the therapeutic effects of these drugs: for example, the use of dapsone for dermatitis herpetiformis and the use of 5-aminosalicylic acid for inflammatory bowel disease.
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PMID:Myeloperoxidase as a generator of drug free radicals. 866 Mar 93

Antineutrophil cytoplasmic antibodies (ANCA) with specificity for proteinase-3 (PR3) are associated with Wegener's granulomatosis, and ANCA directed to myeloperoxidase (MPO) with other idiopathic vasculitides. Inflammation of small-sized blood vessels is a hallmark of systemic lupus erythematosus (SLE). We evaluated the prevalence of ANCA in SLE, their antigenic specificities, and their possible relation to clinical disease patterns and activity. Plasma samples from 84 patients with SLE were tested for ANCA during remission. Plasma samples from the 25 patients who relapsed during a follow-up of 32 months were serially analysed for ANCA in a 6 month period preceding and including the relapse. The presence of ANCA was assessed by indirect immunofluorescence (IIF) and ELISA for antibodies to PR3, MPO, lactoferrin (LF), elastase (HLE) and cathepsin-G (CG). We related the presence of ANCA to disease patterns, activity and duration. ANCA by IIF were difficult to interpret dut to the presence of antinuclear antibodies (ANA). By ELISA, we found no anti-PR3 or anti-HLE. Anti-MPO (n = 7), anti-LF (n = 13) and anti-CG (n = 10) were detected, generally in low titres. The presence of ANCA of defined specificity was not associated with specific clinical subsets. The prevalence of ANCA was higher in patients who developed relapses than in those who did not (P < 0.01). However, levels of ANCA did not fluctuate in the period preceding the relapse. ANCA of various specificities occur in SLE. Their presence is not associated with specific clinical disease entities. The higher frequency of ANCA in relapsing patients compared to those who do not relapse may suggest that ANCA are involved in disease expression. Their diagnostic significance is limited.
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PMID:Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus. 867 May 94

The antithyroid drug propylthiouracil (PTU) is known to cause adverse immunological side effects, such as a lupus-like syndrome and vasculitic disorders. In vitro experiments have established that myeloperoxidase of activated neutrophils can oxidize PTU to the reactive intermediate propyluracil 2-sulfonate PTU-SO3-, and it has been proposed that PTU-SO3- might be responsible for the PTU-associated side effects. Here, using the direct popliteal lymph node assay (PLNA) in mice we found that PTU-SO3-, indeed, induced a T-cell-dependent primary PLN response, whereas the parent compound PTU failed to do so. As shown by adoptive transfer PLNA, splenic T cells of mice that had received four injections of PTU-SO3- mounted a specific secondary response to the reactive metabolite, but not to PTU. When homogenized peritoneal phagocytes, which had been incubated with PTU in vitro, were used as the antigen, a primary response in the direct PLNA was elicited, suggesting that the phagocytes contained the reactive metabolite. Moreover, T cells sensitized to the reactive metabolite PTU-SO3- were detected in mice that were undergoing long-term treatment with PTU plus an additional treatment with phorbol myristate acetate for stimulation of the oxidative metabolism of their phagocytic cells. Together, these findings support the concept that phagocytes oxidize PTU to its immunogenic metabolite, PTU-SO3-, which then, presumably via covalently binding to self-proteins, induces T cell sensitization.
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PMID:T cells ignore the parent drug propylthiouracil but are sensitized to a reactive metabolite generated in vivo. 876 61

We report an unusual case of cytomegalovirus (CMV) interstitial pneumonitis (IP) occurring in a 51-year-old Japanese woman with systemic lupus erythematosus (SLE). She developed hypoxemia after intensive immunosuppressive therapy with prednisolone and cyclophosphamide. Fine crackles were audible in the lower lungs bilaterally. Chest X-ray and computed tomography confirmed the presence of IP. CMV-antigenemia was confirmed by immunological staining of leukocytes using the peroxidase-labeled monoclonal antibody, HRP-C7. Hypoxemia improved gradually on methylprednisolone pulse therapy and gancyclovir, and CMV-antigen positive leukocytes disappeared from the peripheral blood. Data suggest the importance of CMV as a cause of IP in SLE, and the usefulness of the assay for CMV-antigenemia with C7-HRP for rapid diagnosis.
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PMID:Cytomegalovirus-induced interstitial pneumonitis in a patient with systemic lupus erythematosus. 883 9

In this study of antineutrophil cytoplasmic antibody (ANCA)-associated diseases, we determined the prevalence of other autoantibodies and the antigen specificities of ANCA. ANA were common, occurring in 7 of 36 (19%) patients with Wegener's granulomatosis, in 16 of 34 (47%) patients with microscopic polyarteritis, in 6 of 11 (55%) patients with segmental necrotising glomerulonephritis and in 8 of 18 (44%) of those with ANCA-associated systemic vasculitis without renal involvement. ANA were associated more often with pANCA and microscopic polyarteritis than with cANCA (P < 0.05). Patterns were speckled (n = 23), homogeneous (n = 10) or nucleolar (n = 4). Anticardiolipin antibodies were also common, occurring in 10 of 25 (40%) patients with Wegener's granulomatosis, in 8 of 14 (57%) patients with microscopic polyarteritis and in 6 of 18 (33%) of those with a systemic vasculitis. However, anticardiolipin antibodies did not correlate with the presence of ANCA in any of the disease groups. Anti-GBM antibodies were demonstrated in only 2 of 25 (8%) patients with Wegener's granulomatosis, in 1 patient with microscopic polyarteritis (1/14, 7%) and in 1 with segmental necrotising glomerulonephritis (1/11, 9%). All four patients with anti-GBM antibodies had either cANCA or pANCA. In the second part of the study, the target antigens of ANCA were determined in Wegener's granulomatosis, microscopic polyarteritis, systemic vasculitis, inflammatory bowel disease, rheumatoid arthritis and systemic lupus erythematosus (SLE). Of the 19 sera with cANCA, 13 (68%) were directed against proteinase 3; other antigens were myeloperoxidase (1/19, 5%), elastase and lactoferrin together (1/19, 5%), lysozyme (1/19, 5%) or unknown (3/19, 16%). Of the 12 (58%) sera from patients with Wegener's granulomatosis who had cANCA, 7 bound to proteinase 3. Antimyeloperoxidase antibodies were present in 14 of 45 (31%) sera with pANCA; other antigens were proteinase 3 (5/45, 11%), elastase (3/45, 78%), lactoferrin (1/45, 2%), cathepsin G (5/45, 11%) or unknown (17/45, 38%). Antimyeloperoxidase antibodies were common in microscopic polyarteritis (6/14, 43%) and systemic vasculitis (5/16, 31%). However, the majority of target antigens in systemic vasculitis and rheumatoid arthritis with pANCA were not determined. "Atypical" ANCA were present in four patients, one with inflammatory bowel disease (1/8, 13%) and three with SLE (3/15, 20%). The specificities were cathepsin G, cathepsin G plus lactoferrin, or unknown in two sera. A recent report has suggested that bactericidal/permeability-increasing protein may be the target in patients with inflammatory bowel disease.
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PMID:Autoantibodies and target antigens in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. 889 75


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