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Subsets of autoantibodies to extractable nuclear antigens (ENA) as assayed by ELISA correlate with specific clinical abnormalities in SLE.

A clinicopathological study of antinuclear antibodies was performed in 43 patients with SLE. Autoantibodies to double-stranded DNA, measured by RIA, were found in 56% of subjects and were associated with the presence of mesangioproliferative glomerulonephritis, Raynaud's phenomenon and cryoglobulinaemia. Antibodies to extractable nuclear antigens (ENA), when assayed by ELISA, were found in 81% of subjects and were associated with photosensitivity and thrombocytopaenia. Antibodies to RNA-ase-resistant ENA were found in 42% and were associated with cryoglobulinaemia and sclerodactyly, while antibodies to RNA-ase sensitive ENA which had a 49% prevalence were associated with haemolysis and neutropaenia. RNP antibodies (detected by immunodiffusion in 40%) were also associated with photosensitivity. RNP antibody positive and negative sera differed from each other by virtue of their relationship with other autoantibodies, and because RNP-positive sera had significantly higher ENA antibody titres and affinities than did RNP-negative sera. We therefore concluded that various combinations of antinuclear antibodies may predispose to the development of specific clinicopathological lesions in SLE.

Adolescent↗

Erythrocyte CR1 (C3b/C4b receptor) levels and disease activity in patients with SLE.

Fifty-four patients with systemic lupus erythematosus (SLE) were examined for (1) CR1 (C3b/C4b receptor) levels on erythrocytes by an enzyme-linked immunosorbent assay, (2) levels of circulating immune complexes (IC) by a polyethylene glycol precipitation complement consumption method, and (3) concentrations of C3d split products in plasma by intermediate gel rocket immunoelectrophoresis. A preponderance of low CR1 levels was found among patients with SLE (mean 40%, range 13-106) as compared with normal controls (mean 70%, range 24-130) (p less than 0.001). The concentrations of circulating IC were elevated in 38% of 58 samples. The concentrations of C3d were elevated in 72%, and were positively correlated with the levels of IC (tau = 0.28; p less than 0.005) and with disease activity as assessed by a modification of the UCH/Middlesex criteria. Negative correlations were seen between the CR1 numbers and disease activity (p = 0.01), concentrations of circulating IC (tau = -0.14; p less than 0.005), and C3d (tau = -0.21; p less than 0.005). The changes found in CR1 levels on repeated study were, however, relatively small (less than or equal to 27%; median 5), even during periods of changing disease activity.

Adult↗

Prolonged remission of SLE-associated polyradiculoneuropathy after a single course of intravenous immunoglobulin.

Polyradiculoneuropathy is a rare and potentially severe complication of systemic lupus erythematosus (SLE). Treatment is not codified and response to corticosteroid is inconstant. We report the case of a patient with severe SLE-associated polyradiculoneuropathy and autoimmune thrombocytopenia. Dramatic neurologic improvement and correction of thrombocytopenia were observed after a single course of high-dose intravenous immunoglobulin infusions (IVIg, 2g/kg body weight). Our case suggests that IVIg may be effective in the treatment of this unusual condition.

Aged↗

An overview of the treatment of childhood SLE.

Current recommendations for the treatment of pediatric SLE are from uncontrolled trials, case reports, retrospective descriptive data or extrapolation from studies in adults. Glucocorticoids are the mainstay of therapy and the doses depend on the disease severity. Diffuse proliferative glomerulonephritis (DPGN) requires high-dose prednisone for prolonged periods of time. We suggest the addition of azathioprine for DPGN at the time of diagnosis of DPGN and reserve cyclophosphamide for refractory cases. While we do not recommend the routine use of cyclophosphamide in this or other forms of lupus nephritis, others advocate the aggressive use of intravenous cyclophosphamide and prednisone. Severe central nervous system disease should be treated with high dose prednisone and immunosuppressive agents are reserved for life-threatening disease or steroid failure or dependency. We suggest the routine use of hydroxychloroquine in all cases of SLE at a dose of 5 mg/kg/day (maximum of 400 mg/day). Methotrexate has been recently used with some success in both children and adults, the safety profile appears to be very good and therefore further studies of this drug are warranted. Collaboration in the development of a limited number of defined treatment protocols and large scale collection of data on a multicenter and multinational basis is needed if we hope to improve the outcome of patients with severe disease.

Child↗

The role of hsp90 in SLE.

The heat shock proteins are a group of evolutionarily conserved proteins with important physiological functions, whose synthesis is enhanced by elevated temperature or other stresses. A role for one or more of these proteins in human autoimmune disease has been extensively discussed. This review considers the evidence of a role for hsp90 in systemic lupus erythematosus (SLE) where overexpression of this protein, its surface localization and auto-antibodies to it have been observed in both human patients and in the MRL/lpr mouse model of SLE.

Animals↗

Development of a DNA-adsorbent for the specific removal of anti-DNA autoantibodies in systemic lupus erythematosus (SLE).

Autoantibodies against DNA are of primary importance for the diagnosis and pathogenesis of systemic lupus erythematousus (SLE). The level of anti-DNA antibodies correlates well with the disease activity and renal involvement. In such patients the removal of anti-DNA antibodies from plasma may lead to a clinical improvement. For this reason an adsorbent was made by covalent coupling of calf thymus DNA to a solid support based on ethylene dimethacrylate cross-linked hydroxethyl methacrylate. Up to 2.5 mg of DNA were immobolized to 1 ml of the support activated chemically by aminosilane and glutaraldehyde. The incubation of 40 ml of SLE plasma with 1 ml of the adsorbent resulted in a 50% decline in anti-DNA activity. There was no release of immobilized P-32-DNA into the plasma. Biocompatibility, sterilisation, and reapplication (without loss of binding capacity) of the adsorbent could be demonstrated. We concluded that the adsorbent may be suitable for treatment.

Autoantibodies↗

[Assessment of tissue microcirculation in patients with aseptic necrosis of femur heads in systemic lupus erythematosus (SLE)].

AIM: To study microcirculation in the tissues above the hip joints with and without aceptic necrosis of the femur head for diagnosis of necrosis stages. MATERIALS AND METHODS: 22 SLE patients were examined for blood flow above the region of affected and intact (control) hip joints using clearance of Xe-133 from the intratissue deposit. Basal circulation and factors of its regulation were investigated with laser dopplerflowmetry. RESULTS: Effective skin blood flow above the hip joints with necrosis stage I significantly differed from that of the control. Basal skin blood flow above the hip joints in suspected stage I of aceptic necrosis differed significantly from the control and that in stage II osteonecrosis. CONCLUSION: The study of tissue microcirculation above the hip joints in SLE patients with aceptic necrosis of the femur heads allows making diagnosis both at early and late stage of osteonecrosis.

Blood Flow Velocity↗

Autoantibodies in SLE. Disease associations.

Antinuclear antibodies are an almost universal feature of SLE. Over the years they have been the subject of intensive study to understand the underlying pathogenesis of the disease. It is clear that ANA in the context of lupus are directed against highly selected targets and are not just the result of nonspecific polyclonal B cell activation. Frequently they react with components of nucleoprotein complexes involved in important cellular processes which are very specific targets for autoimmunity in this condition. The antibodies themselves belong primarily to the IgG1 and IgG3 subclasses of immunoglobulin, are high affinity, occur in large amounts, have important associations with particular HLA class II genes and show all the features of an antigen-driven, T cell-dependent immune response. Although at first glance there is a wide range of antibody specificities associated with SLE, in the individual patient the autoantibody profile is much more restricted. Methods to detect these antibodies have provided the clinician with valuable tools to assist both in diagnosis and assessment of lupus patients. It has been possible to recognise distinctive serological subsets within the spectrum of lupus which are associated with certain patterns of disease expression. This can be helpful in determining both disease classification and prognosis.

Antibodies, Antinuclear↗

Anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus. Prevalence and clinical associations. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: To test the prevalences and the clinical associations of anticardiolipin (aCL) and anti-beta2GPI (abeta2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). METHODS: 574 SLE patients from 7 European countries were tested for aCL and abeta2GPI by ELISA methods. RESULTS: aCL of IgG, IgM, and IgA isotypes were detected in 22.8%, 14%, and 13.9% of the patients, respectively. IgG and IgM abeta2GPI were detected in 20% of the patients. The presence of aCL was highly associated with the presence of abeta2GPI. Medium-high titer IgG aCL and abeta2GPI were associated with thrombosis, with similar sensitivity, specificity, and positive predictive value. When present at medium-high titer, IgG aCL were associated with thrombocytopenia, IgM aCL with hemolytic anemia, and cerebrovascular accidents. IgA aCL with livedo reticularis and Raynaud's phenomenon. CONCLUSIONS: aCL, when present at medium-high titer, are as important as abeta2GPI, as a risk factor for thrombosis. Medium-high titer aCL, but not abeta2GPI, are associated with other clinical features of the antiphospholipid syndrome.

Adolescent↗

The value of tests for antibodies to DNA in monitoring the clinical course of SLE. A long-term study using the Farr test and the DNA counterimmunoelectrophoretic method.

Serial serum samples from fifteen patients with SLE, taken over periods varying from 6 months to 6 years, were tested for DNA binding capacity, DNA electroprecipitins (DNA-EP) and C'3 level to assess the value of these investigations in reflecting clinical disease activity. Patients with renal involvement showed a good correlation between high levels of DNA binding, low serum C'3 and disease activity and typically, their DNA-EP was negative. By contrast, patients without renal involvement in whom vasculitis was prominent, showed a poor correlation of DNA binding capacity to changes in the state of their disease although the DNA-EP test was persistently positive. It was also apparent that both the DNA-BC and C'3 can show marked variation in response to alterations in treatment without accompanying clinical change. Although these serological tests, particularly the DNA binding capacity are of recognized value in the diagnosis of SLE, they serve most usefully as guides to long-term management when they can be related to the clinical pattern of the disease.

Antibodies↗

[Pure red cell aplasia induced by clomipramine hydrochloride in a patient with SLE].

A 48-year-old woman, who had been suffering from systemic lupus erythematosus (SLE), developed normochromic normocytic anemia after receiving clomipramine hydrochloride. Her reticulocyte count was low, and a bone marrow aspirate revealed erythroid hypoplasia without involvement of other cell lines. Thus a diagnosis of pure red cell aplasia (PRCA) was made. The anemia gradually resolved following withdrawal of the drug. Although several drugs are known to cause PRCA, this is the first time that clomipramine hydrochloride has been reported to have such an effect. The underlying SLE in this case suggested the possible immunological pathogenesis of drug-induced PRCA.

Antidepressive Agents, Tricyclic↗

Recalcitrant trichophytic granuloma associated with NK-cell deficiency in a SLE patient treated with corticosteroid.

Although deep trichophytic infection often occurs in immunocompromised patients, the immune deficiency in such patients has not been clarified. A 28-year-old man who suffered from recalcitrant trichophytic granuloma and tinea universalis during treatment for SLE with corticosteroid is described here to define the immunological abnormalities. In addition to routine immunological tests, we evaluated the patient's innate and specific immune functions to dermatophytes, including T cell, natural killer (NK) cell and neutrophil functions and activation of the complement cascade. We measured the minimum inhibitory concentration (MIC) of itraconazole for the isolated fungus and its concentrations in the patient's serum and pus. Trichophyton (T.) rubrum was constantly isolated from the exudates of the patient's skin lesions, although the concentrations of itraconazole in his serum (198 ng/ml) and lesions (210 ng/ml) were sufficient to inhibit the growth of the isolated fungus in vitro. Specific cell-mediated immune responses, determined by T cell stimulation and IFN-gamma production, were evoked following stimulation with trichophytic antigens. The patient's innate immunity, assessed by activation of the complement cascade and neutrophil-mediated phagocytosis, was not impaired. The number of circulating NK cells was markedly decreased (0.2% of the peripheral blood mononuclear cells), and was associated with low NK cell activity against K-562 cells even though lymphopenia had improved. The deficiency of innate immunity mediated by NK cells might be responsible for a part of the persistence of trichophytic granuloma in our case. Dermatophytes usually affect the horny layer of the skin and do not invade the living layers because the host immune system uses various mechanisms to eliminate the fungi. Both specific T cell-mediated immunity and nonspecific immunological mechanisms provide host defense against fungal infections. An adaptive immune response is usually preceded by innate immune responses mediated by neutrophils, NK cells, and circulating proteins such as complement components and anti-microbial peptides. However, in patients with localized or systemic immunological defects, granulomatous cutaneous infection of dermatophytes mostly caused by trichophytic fungi may occur [1]. Trichophytic granuloma includes Majocchi's granuloma [2] and disseminated trichophytic granuloma [3]. Recently, we experienced a patient with trichophytic granuloma and tinea universalis caused by Trichophyton (T.) rubrum infection during treatment with corticosteroid for systemic lupus erythematosus (SLE). We describe the clinical details of this patient, focusing on his immunological defects which led to the persistence of the fungal infection.

Adult↗

[A case of SLE presenting the features of antiphospholipid antibody syndrome during a treatment for complicated cryptococcal meningitis].

A 39-year-old woman had developed systemic lupus erythematosus(SLE) at the age of 29. She had a long history of immunosuppressant therapies such as corticosteroid. On admission, she presented a headache due to the cryptococcal meningitis which was confirmed by lumbar puncture. Combined medications of amphotericin B and fluconazole were not effective, and combined amphotericin B and flucytosine were replaced. Prednisolone and methotrexate had been tapered gradually. Fifty days after the initial treatment for meningitis Cryptococcal neoformans was not observed in the cerebrospinal fluid. Sixty days after the treatment, thrombocytopenia was observed with positive lupus anticoagulant and anticardiolipin antibody. Following which, thrombophlebitis occurred in the left brachium. We suggest that the provoked pathoimmunological reaction such as antiphospholipid antibody syndrome during the treatment for meningitis needs to be cared during the course of SLE.

Adult↗

Specificity of SLE serum antibody for single-stranded and double-stranded DNA configuration.

The solid phase immunoassay for the measurement of serum antibody to double and single-stranded DNA is described. The technique allows a more accurate definition of the antibody specificity of SLE sera as defined by inhibition techniques. The clinical usefulness of immunologic assays in the management of patients with SLE is described, including measurement of urine light chain protein concentration. A core discussion is provided to illustrate how such a panel of tests is used in management.

Adolescent↗

Studies on the nature of circulating DNA in systemic lupus erythematosus (SLE).

The isolation and purification of DNA from the sera of patients with SLE is described. Buoyant density determinations of this DNA using CsCl gradients suggest in some cases that it may be of endogenous origin. DNA from the synovial fluid of an SLE patient with septic arthritis was also shown to have a buoyant density of human DNA as well as being of considerable size variation. In addition, this synovial fluid contained antibody to DNA and evidence of DNA:anti-DNA complexes, suggesting that immune complexes composed of human DNA and antibody may be involved in the pathogenesis of the arthritis. Also described are preliminary experiments characterizing the conformation of the DNA present in DNA:anti-DNA immune complexes.

Animals↗

Recurrence of SLE in transplanted kidneys: a follow-up transplant biopsy study.

Renal transplant biopsies were obtained from 16 patients with systemic lupus erythematosus 6 months to 11 years post-transplant. Eight biopsies were taken on clinical grounds while eight were elective. Histopathological findings suggesting recurrent lupus nephritis were found in seven biopsies, five of which were taken on clinical indication. By light-microscopy, five graft biopsies showed proliferative glomerulopathy and two glomerulosclerosis. Immunofluorescence was positive for IgM and C3 in a finely granular pattern in all biopsies, for C1q in three, but for IgG in only two. Electron-dense deposits were found in all seven biopsies with predominantly subendothelial location. All but one patient had clinical signs of renal involvement, but only three had extrarenal symptoms and three had serological signs of active SLE. Upon increased immunosuppressive therapy, renal and serological signs improved but one graft was later lost due to recurrent SLE nephritis.

Adolescent↗

Lupus peritonitis presented as vague abdominal complaints in a SLE patient.

A 40-yr-old Caucasian woman who had been suffering from systemic lupus erythematosus (SLE) since five years developed vague abdominal complaints whilst under treatment with a low dose of steroids. She had been admitted because of vomiting and abdominal tenderness. The ESR and CRP levels were rising and the C4 level had been persistently low in the preceding months. Normal non-invasive procedures did not allow a diagnosis to be made. Therefore exploratory laparotomy was performed and revealed a non-bacterial peritonitis and an oedematous jejunum. She responded well to a high dose of prednisone. Serositis of the peritoneum as well as bowel vasculitis may be a rare manifestation of SLE despite apparent control of other lupus manifestations. In this patient serositis flares were associated with a rise in CRP level.

Adult↗