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)

Systemic Lupus Erythematosus (SLE) is a disease with multiorgan involvement and multiple autoantibody production including antineutrophil cytoplasmic antibodies (ANCA). Despite its reported prevalence in more than one third of SLE patients, the role of ANCA in the pathogenesis or otherwise in SLE remains unresolved. 131 SLE patients had been previously studied for various serologic parameters of disease activity. Their cumulative organ involvement in the course of their disease had also been determined and the Lupus Activity Index (LAI) calculated. Their stored sera were then screened for the presence of ANCA by two methods viz Indirect immunofluorescence (IIF) and also enzyme-linked immunosorbent assay (ELISA). ANCA was present in 24.8% of these SLE patients. The atypical ANCA pattern was predominant and accounted for an overall of 20.6%. Anti-MPO and anti-PR3 were detected in 1.5% of patients respectively. No association was found between ANCA positivity and disease activity. There was also no association of ANCA with specific organ involvement. Despite the high prevalence of ANCA especially the atypical variant in SLE, they probably represent only one of the wide repertoire of autoantibodies found in this disease. Routine testing for ANCA in lupus patients is therefore not recommended.
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PMID:Antibodies in systemic lupus antineutrophil cytoplasmic erythematosus: prevalence, disease activity correlations and organ system associations. 1572 83

Rituximab is a genetically engineered chimeric monoclonal immunoglobulin (Ig)G1 antibody. It binds the CD20 trans-membrane surface antigen expressed by mature B cells but not by antibody secreting plasma cells, and removes the cells by activating complement, inducing cell-mediated lysis, and by apoptosis. Mainly used for the treatment of non-Hodgkin's lymphomas, rituximab has recently been tried with favourable responses in rheumatoid arthritis, systemic lupus erythematosus, and other chronic immunological diseases. Wegener's granulomatosis (WG) is a granulomatous vasculitis with high morbidity and mortality. It is thought that anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for proteinase 3 (PR3) are possibly involved in the pathogenesis of the disease. Conventional therapy with cyclophosphamide and corticosteroids generally succeeds in inducing remission, but relapses frequently follow. Among the biological agents, tumour necrosis factor-alpha (TNF-alpha) inhibitors have been tried with some success. Based on a case report we recently treated three refractory WG patients with rituximab and achieved almost complete but temporary remission. CD20+ cells disappeared rapidly in peripheral blood, only to rise prior to subsequent disease flares occurring at 34, 63, and 54 weeks, respectively (Figure 1). A new flare occurred in one patient at 86 weeks. At the end of the observation periods (54, 102, and 120 weeks), only one patient had proteinuria. Chest radiographs became normal in two patients, while infiltrates remained unchanged in the third. Granulomatous retro-orbital or sinus masses in two patients seemed unresponsive to therapy.
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PMID:Anti-CD20 therapy of treatment-resistant Wegener's granulomatosis: favourable but temporary response. 1613 30

Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (alpha1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low alpha1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease.
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PMID:Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides. 1620 47

Much like other autoantibodies (eg, anti-double stranded DNA in systemic lupus erythematosus or antiglomerular basement membrane antibodies in Goodpasture's syndrome), antineutrophil cytoplasmic antibodies (ANCA) have provided doctors with a useful serological test to assist in diagnosis of small-vessel vasculitides, including Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and their localised forms (eg, pauci-immune necrotising and crescentic glomerulonephritis). 85-95% of patients with Wegener's granulomatosis, microscopic polyangiitis, and pauci-immune necrotising and crescentic glomerulonephritis have serum ANCA. ANCA directed to either proteinase 3 or myeloperoxidase are clinically relevant, yet the relevance of other ANCA remains unknown. Besides their diagnostic potential, ANCA might be valuable in disease monitoring. In addition, data seem to confirm the long-disputed pathogenic role of these antibodies. Present treatments for ANCA-associated vasculitis are not free from side-effects and as many as 50% of patients relapse within 5 years. Accurate understanding of the key pathogenic points of ANCA-associated vasculitis can undoubtedly provide a more rational therapeutic approach.
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PMID:Antineutrophil cytoplasmic antibodies. 1687 69

Establishing a diagnosis of systemic rheumatic disease requires an integration of a patient's symptoms, radiological findings, and the result of biological tests. Clinicians often try to rely heavily on objective measures such as the presence of an autoantibody. Few tests are highly sensitive, though the antinuclear antibodies in systemic lupus erythematosus (SLE) and the erythrocyte sedimentation rate in polymyalgia rheumatica. Some tests are highly specific: anti-PR3 and anti-MPO among patients with Wegener granulomatosis (and related vasculitides), anti-ds DNA among patients with SLE and anti-CCP in rheumatoid arthritis. Medical literature may overestimate the diagnostic utility of many commonly ordered tests for rheumatic diseases. Serum rheumatologic tests are generally most usefull for confirming a clinically suspected diagnosis.
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PMID:[Clinical utility of serum diagnostic tests for rheumatic diseases]. 1795 25

Gout is caused by monosodium urate (MSU) crystal-induced inflammation of the joints and periarticular tissues. MSU crystals activate the NOD-like receptor (NLR) NALP3, which functions as a pattern recognition receptor (PRR). Activated NALP3 mediates interleukin-1b (IL-1b) generation from its inactive pro-form, resulting in the activation of further cells and an IL-8-mediated neutrophil influx into the joint. Based on these new findings on the pathophysiology of gout, an open pilot study has recently demonstrated successful treatment of gout with the soluble IL-1R antagonist anakinra in 10 patients. The physiological role of MSU crystals might be that of a danger signal in peripheral tissues, where they stimulate dendritic cell maturation. The role of PRRs such as the NLR is underlined by NALP3 mutations causing hereditary autoinflammatory syndromes and NOD2 polymorphisms as genetic risk factors for Crohn's disease. In addition to the recognition of danger-associated molecular patterns (e.g. MSU), PRRs confer autoantigen recognition and activation of the innate and adaptive immune system in autoimmune diseases. Detection of RNA and DNA-containing immune complexes by toll-like receptors inducing B-cell activation in systemic lupus erythematosus and of proteinase 3 by the protease-activated receptor-2 inducing dendritic cell maturation in Wegener's granulomatosis have recently been reported.
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PMID:[New aspects of the pathogenesis of gout. Danger signals, autoinflammation and beyond]. 1829 53

We report a case of pauci-immune proliferative necrotizing and crescentic glomerulonephritis in a patient with systemic lupus erythematosus (SLE) who presented with a nephrotic syndrome, while SLE was clinically and serologically quiescent. Immunofluorescence and electron microscopy examination of the kidney biopsy failed to reveal any significant deposit of immunoglobulins as well as of complement C3 and C1q, excluding lupus nephritis as the determinant of crescentic glomerulonephritis. Anti-myeloperoxydase (MPO) as well as anti-proteinase 3 (PR3) antibodies were absent in the serum. An immunosuppressive regimen including corticosteroids and IV cyclophosphamide led to a dramatic decrease of proteinuria. We conclude that necrotizing glomerulonephritis unrelated to lupus nephritis may occur in a patient with quiescent SLE. An underlying dysfunction of cell-mediated immunity might explain the association of pauci-immune crescentic glomerulonephritis and SLE.
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PMID:Pauci-immune necrotizing and crescentic glomerulonephritis in a patient with systemic lupus erythematosus. 1839 4

The objective of the study was to evaluate the clinical features, response to treatment, and long-term outcome of subglottic stenosis (SGS) in a series of patients diagnosed as having Wegener's granulomatosis (WG) at a single institution. Subglottic stenosis developed in 6 out of 51 (11.7%) patients, in four of them in the absence of other features of active disease, and was the symptom that leads to WG diagnosis in three cases. In two cases, SGS began while the patients were receiving systemic immunosuppressive therapy for disease activity involving other sites. PR3-ANCAs were positive in four cases. An urgent tracheostomy was needed in two patients. Four patients achieved SGS clinical remission on standard treatment with glucocorticoids and cyclophosphamide, but three of them experienced repeated local relapses and required additional immunosuppressive therapy and mechanical dilations. In one case, a local relapse was successfully managed with endotracheal dilation of the stenotic segment and intralesional injection of a long-acting corticosteroid plus mechanical dilation of the stenotic segment (ILCD) without adding supplemental immunosuppressant drugs. Two patients with isolated SGS were also successfully managed with ILCD alone and did not require the institution of systemic immunosuppressive therapy. One patient underwent open surgical repair when the disease was under control. Our data suggest that Subglottic stenosis often occurs or progresses independently of other features of active WG, and that ILCD may be a safe alternative to conventional immunosuppressive therapy in patients who develop SGS in the absence of other features of active disease, allowing reducing the treatment-related toxicity.
Lupus 2008 Sep
PMID:Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis. 1875 65

A 26-year-old female with systemic lupus erythematosus was admitted because of dyspnea and progressive lower extremity edema. Laboratory testing showed blood urea nitrogen levels of 147 mg/dL, creatinine of 6.7 mg/dL, serum albumin of 1.7 g/dL and the daily protein loss was 12.7 g. Her C3 level was 60.4mg/dL and C4 level was 10.2 mg/dL. The antinuclear antibody titer was 1:320, with a homogeneous pattern, but she was negative for anti-dsDNA. ELISA testing for anti-PR3 antibodies and anti-MPO antibodies were all negative. She was also negative for circulating lupus anticoagulant. Renal biopsy revealed diffuse proliferation of glomerular cells, but immunofluorescent microscopy showed no immune deposits and electron microscopy revealed only scanty electron-dense deposits. She received 1 g/day of methylprednisolone intravenously for 3 days, followed by 60 mg/day of prednisolone. She was discharged with serum creatinine decreased to 4.7 mg/dL, and a great improvement in dyspnea. Diffuse proliferative lupus nephritis that contains little or no subendothelial deposits is rare. The differential diagnosis, possible mechanisms and treatment are discussed.
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PMID:Pauci-immune lupus nephritis: a case report. 1918 84

The aim of this study was to evaluate a novel third-generation enzyme-linked immunosorbent assay (ELISA) for the high-sensitivity detection of autoantibodies to proteinase-3 (PR3) in patients with Wegener's granulomatosis (WG). First- and second-generation ELISA for the detection of antineutrophil cytoplasmic antibodies (ANCA) frequently demonstrate insufficient sensitivity due to inadequate presentation of autoantigenic epitopes. Human PR3 was immobilized on the solid phase of ELISA plates by anchoring technique. Anti-PR3 reactivity was measured in 34 C-ANCA positive patients with WG, 11 MPO-ANCA-positive patients with other autoimmune vasculitides, 65 patients with systemic lupus erythematosus (SLE), and 137 healthy blood donors. Thirty-three of 34 patients with WG (97.1%) showed positive anti-PR3 IgG antibody reactivity. None of 11 MPO-ANCA positive vasculitis patients, none of 137 blood donors, and 3 of 65 SLE patients expressed elevated IgG reactivity to PR3 (specificity: 98.4%). Comparison with another third-generation ELISA did not reveal different qualitative results. However, there was no significant correlation between quantitative results of both assays. Receiver operating characteristic (ROC) curve analysis revealed a significantly better assay performance compared with first (direct)- and second (capture)-generation assays (P = 0.011 and P = 0.001, respectively). Third-generation (anchor) anti-PR3 ELISA exhibit significantly higher sensitivity than previous generation assays. Anchoring of PR3 renders the granulocyte protein more autoantigenic compared with direct or capture immobilization.
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PMID:High-sensitivity detection of autoantibodies against proteinase-3 by a novel third-generation enzyme-linked immunosorbent assay. 1975 30


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