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)

Current clinical practice relies heavily on serologic testing for the prompt and accurate diagnosis of rheumatic diseases. Serologic testing should be used to support the findings of the history and physical examination, and, in some cases, to monitor disease activity. The inflammation of the rheumatoid arthritis (RA), polymyalgia rheumatica, and temporal arteritis can be assessed by the erythrocyte sedimentation rate (ESR). The C-reactive protein (CRP, an acute-phase protein) test, which is newer, correlates more closely than ESR with clinical and radiographic parameters of RA inflammation. The rheumatoid factor test is nonspecific as a screen for RA, and some argue that it is also insensitive (accounting for the existence of "seronegative" RA). High titers of rheumatoid factor are associated with progressive joint inflammation, erosions, and disability. Antinuclear antibody (ANA) tests are likewise nonspecific, but ANA subtypes have proved to be very specific for subtypes of connective tissue diseases. Examples are the presence of anti-DNA antibody in systemic lupus erythematosus; anti-centromere antibody in the CREST syndrome of scleroderma; anti-histone antibody in drug-induced lupus; and anti-Ro antibody in neonatal lupus. Anti-neutrophil cytoplasmic antibodies (ANCA) are a new group of auto-antibodies seen in Wegener's granulomatosis. Brief case descriptions are presented to illustrate appropriate selection of these antibody tests as well as tests for antiphospholipid antibodies and cryoglobulins.
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PMID:Selection and use of laboratory tests in the rheumatic diseases. 860 22

The clearance of nucleosome core particles and H1-stripped chromatin from the circulation of mice was examined. Radiolabeled chromatin preparations were injected into mice, and blood samples were obtained over 60 min. The animals were then killed, and the selected organs were collected and radioactivity was measured. The acute phase response (APR) was induced by i.p. injections of casein before some clearance studies. Serum amyloid P component, the major acute phase protein in mice, increased from 27 microg/ml to 339 microg/ml during the acute phase. The rate of chromatin clearance decreased during the acute phase in C57BL/10J mice. At 5 min, 18% +/- 3% of the originally measured radioactivity remained in control animals compared with 49% +/- 2% in acute phase animals (p < 0.001). Co-injection of either serum amyloid P component or C-reactive protein, the major acute phase protein in humans, caused a decrease in the rate of chromatin clearance similar to that observed following the induction of the APR. APR induction also caused a higher percentage of the chromatin to localize in the liver compared with the spleen, with the ratio changing from 10.2 +/- 0.7 to 16.1 +/- 1.9 (p < 0.004). In addition, the APR caused a decrease in the percentage of chromatin localized in the kidney. The lack of radioactivity associated with cells in the circulation indicates that complement is not a major factor in the clearance mechanism of chromatin. These findings suggest that the APR produces major changes in the rate and path of chromatin clearance. These changes may protect against deposition of chromatin in target organs of systemic lupus erythematosus.
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PMID:The effect of acute phase proteins on clearance of chromatin from the circulation of normal mice. 864 25

To investigate the contribution of IL-11 and LIF to acute-phase protein (APP) production, we first analysed the effects of IL-11 and LIF on production of C-reactive protein (CRP), fibrinogen, and haptoglobin by human primary hepatocytes. We also measured the serum levels of IL-11, LIF, and CRP in serum from patients with inflammatory rheumatic diseases to assess the role of these cytokines in the APP response in vivo. We included patients with conditions associated with a high APP response such as rheumatoid arthritis (RA) or spondylarthropathy (SpA), and others usually associated with a weak APP response such as systemic lupus erythematosus (SLE), in order to investigate whether these cytokines could account for the differences in APP responses. Our results showed that IL-11 and LIF induced only minimal stimulation on production of APP by human primary hepatocytes compared with IL-6, known as the major inducer. Serum levels of CRP were elevated in RA and SpA, and significantly higher than in SLE patients. Despite the presence of a high APP response in some of our patients and despite the fact that we used sensitive assays to measure IL-11 and LIF, serum levels of both cytokines were not detected in any of the tested sera. In conclusion, our results show that circulating levels of IL-11 or LIF do not contribute significantly to the production of APP in vivo, and that they do not account for the difference in APP response between SLE and other inflammatory rheumatic diseases.
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PMID:Circulating levels of IL-11 and leukaemia inhibitory factor (LIF) do not significantly participate in the production of acute-phase proteins by the liver. 870 31

IgG antibodies to cardiolipin and beta 2-glycoprotein I were looked for using an enzyme-linked immunosorbent assay (ELISA) in 19 patients with giant cell arteritis (meeting 1990 American College of Rheumatology criteria), including 16 with concomitant polymyalgia rheumatica (meeting Bird's criteria) and in three patients with isolated polymyalgia rheumatica. IgG anti-cardiolipin antibodies were demonstrated in eight patients (36%) and IgG anti-beta 2-glycoprotein I antibodies in two patients (9%) including one without anti-cardiolipin antibodies. Titers of anti-cardiolipin antibodies ranged from 27 to 190 units of IgG antiphospholipid antibodies (UGPL) (mean 71 UGPL). Of the eight patients with anti-cardiolipin antibodies, two had giant cell arteritis without polymyalgia rheumatica and six had polymyalgia rheumatica with clinical (n = 2) or histologic (n = 4) evidence of giant cell arteritis. None of the three patients with polymyalgia rheumatica but no giant cell arteritis had anti-cardiolipin or anti-beta 2 glycoprotein I antibodies. The VDRL was negative in the 14 patients who had this test. Tests for lupus anticoagulant were performed routinely, always with negative results. Among giant cell arteritis patients, those who tested positive for anticardiolipin antibody had significantly higher values for the erythrocyte sedimentation rate (p < 0.006) and for serum C-reactive protein (p < 0.03) and fibrinogen values (p = 0.05), and a trend toward higher platelet counts, as compared to those who tested negative for anticardiolipin antibody. The mean daily prednisone dose at the time of sampling was significantly lower in giant cell arteritis patients with anti-cardiolipin antibodies (p < 0.05); this difference may account for the apparent correlation between anti-cardiolipin antibodies and laboratory markers for inflammation. These data, as well as findings from serial measurements, suggest that anti-cardiolipin antibodies are present early in the course of giant cell arteritis and disappear within a few weeks of initiation of corticosteroid therapy in a dose of more than 25 mg prednisone per day. In this study, only one patient without anticardiolipin antibodies developed a cerebrovascular accident. Positive tests for anti-cardiolipin antibody or anti-beta 2 glycoprotein I antibody in a patient with polymyalgia rheumatica suggest a diagnosis of concomitant giant cell arteritis, which is usually symptomatic.
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PMID:Antibodies to cardiolipin and beta 2 glycoprotein I in patients with polymyalgia rheumatica and giant cell arteritis. 873 42

Biological markers of inflammation are useful for the diagnosis and the monitoring of inflammatory rheumatisms and connective tissue diseases. These markers are not specific, and often poorly correlate with the long term evolution of the disease. C-reactive protein (CRP) is a sensitive marker, and is used to monitor inflammatory and infectious diseases. In rheumatoid arthritis (RA), CRP correlates with disease activity and response to therapy, and CRP levels are influenced by disease-modifying drugs and corticosteroids. Serum amyloid A (SAA) is another acute phase protein (APP) which appears in RA as a more sensitive marker than CRP. Several antinuclear antibodies serve as markers of systemic disorders; they are not implicated in the disease by themselves, but their production could be related to the genetic background underlying the pathogenesis of the disease. In systemic lupus erythematosus (SLE), the titer of anti-ds DNA antibodies often correlates with disease activity. DNA is poorly immunogenic and the production of anti-ds DNA antibodies could be linked to the association of DNA with more immunogenic protein antigens. Cellular DNA is associated with proteins in nucleosomes and it now appears more appropriate to consider the anti-DNA antibody production as a response to a DNA-protein complex. Antibodies can be directed to histones and DNA-protein complexes such as transcription or replication complexes. Antibodies to ribonuclear proteins are associated with different disease subsets and help to define the prognosis in SLE and connective tissue diseases. The identification of antibodies directed against proteins and RNA components is still a field of research.
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PMID:Biological markers in inflammatory rheumatic diseases. 874 80

Cytokines are believed to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, for tumour necrosis factor alpha (TNF-alpha) both beneficial and deleterious effects have been reported. To obtain information about the involvement of this cytokine in the pathophysiology of SLE, serum levels of TNF-alpha, the soluble forms of the 55 and 75 kDa tumour necrosis factor receptors (TNF-R55 and TNF-R75), and interleukin-6 (IL-6) were measured by ELISA in nine female patients over a period of 2 yr. Compared to healthy controls, levels of TNF-alpha (median 47 pg/ml, range < 15-222 pg/ml), TNF-R55 (median 1.9 ng/ml, range 0.8-10.8 ng/ml), TNF-R75 (median 4.7 ng/ml, range 1.5-15 ng/ml) and IL-6 (median 3.5 pg/ml, range < 3.5-52 pg/ml) were significantly elevated in SLE patients (P < 0.0001 vs controls in all cases). There were strong correlations between TNF-alpha and its soluble receptors (P < 0.0001). Moreover, TNF-alpha and both TNF-Rs strongly correlated with clinical and serological parameters of disease activity, such as the European Consensus Lupus Activity Measurement (ECLAM) score, anti-dsDNA antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anaemia (P < 0.0001 for all comparisons). TNF-alpha and TNF-R75 also correlated with IL-6 (P < 0.0001). However, no correlation between IL-6 and ECLAM was found, and the correlation of IL-6 with anti-dsDNA was relatively weak; in contrast, IL-6 correlated strongly with CRP and ESR (P < 0.0001). Although these data do not allow us ultimately to discriminate between beneficial and deleterious effects of TNF-alpha, they nevertheless suggest a central role for the TNF system in the pathophysiology of SLE.
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PMID:Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus. 894 91

In order to get a better insight into cytokine network regulation in systemic lupus erythematosus (SLE), we analyzed levels of interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in the sera from 36 SLE patients. Moreover, C-reactive protein (CRP), alpha-1-acid-glycoprotein (AGP), and alpha-1-antichymotripsin (ACT) serum levels were evaluated. Serum levels of IL-10 and IL-6 were significantly increased when compared with healthy controls. TNF-alpha and IFN-gamma did not differ from normal values. We established the relationship between IL-10 and IL-6 as well as between IL-10 and TNF-alpha. None of the analyzed cytokines correlated with the acute phase protein levels. Based on the obtained data, we conclude that IL-10 may play the superior regulating role in SLE. A lack of correlation between the cytokines and acute phase proteins suggests their independence from cytokine regulation.
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PMID:Cytokine concentration in serum of lupus erythematosus patients: the effect on acute phase response. 924 16

Thirty-one consecutive patients with SLE were screened for antinuclear antibody (ANA), anti-DNA antibodies, extractable nuclear antigen antibodies (anti-ENAs) including anti-Sm, anti-RNP, anti-SSA (anti-Ro), anti-SSB; (anti-La), anti-Scl-70, rheumatoid factor (RF), C-reactive protein (CRP), C3 and C4 levels, anti-cardiolipin antibodies (aCL), biologically false positive serological test for syphilis (BF-STS) using VDRL test and Coombs' test. The age of the patients ranged from 11 to 52 year with a median of 29 year; female to male ratio of 5:1. There were 21 Kuwaitis, four Egyptians, three from the Indian subcontinent, two Filipinos and one Syrian. Main clinical categories of SLE were: mild cutaneous SLE in 12 (38.7%), clinical antiphospholipid syndrome (APS) secondary to SLE in 8 (25.8%), haematological manifestations of SLE in 5 (16.1%), renal lupus in four (12.9%), neuropsychiatric in three (9.7%), others (6.4%). Clinical features overlapped in several patients. ANA was positive in 96.8% (mean value 891.61 units/ml), anti-DNA in 35.5% (mean value 56.4 units) that was lower than expected and could be due to selection bias as the patients were from a rheumatology clinic, anti-ENA in 42%, anti-Sm 13% that was lower than other non-Caucasian populations, anti-RNP 13%, anti-SS-A in 35.5%, anti-SS-B in 19.4%, Scl-70 in 13%, CRP in 71% (moderate 58%, very high 13%); C3 mean 1.52 mg/ml (3.2% low levels), C4 mean 0.35 mg/ml (32% low levels), anticardiolipin mean GPL 35.35 units (high 58%), mean MPL 10.61 units (high 26%), BF-STS in 6%, Coombs' test in 6%, RF positive in 36%. The only significant positive clinical associations observed were those of renal involvement with anti-DNA antibodies (P = 0.042), and clinical antiphospholipid antibody syndrome with aCL antibodies (P = < 0.05).
Lupus 1997
PMID:Serological characteristics of systemic lupus erythematosus from a hospital-based rheumatology clinic in Kuwait. 936 26

We report a 38-year-old man systemic lupus erythematosus who presented with an acute onset of paraplegia and urinary retention. The man had a 12-year history of nodular cutaneous mucinosis and arthralgia. In 1994, he was admitted to our hospital with a sudden onset of weakness and numbness of the right leg followed by an emergence of similar symptoms in the left leg. His elder sister had died at 16 years of age after suffering from systemic lupus erythematosus for 6 years. On examination, the patient had skin rash on his chest, back, head, forehead, and extremities. The neurological examination revealed that his tongue deviated to the right on protrusion. The muscle power was reduced to 2-3/5 in the right leg and to 4/5 in the left leg. The sensory disturbance was noted in the lower extremities with predominant involvement of the right leg. Reflexes were increased in the right biceps, triceps, both patellas, and Achilles tendons. Babinski sign was noted bilaterally. Urinary retention and constipation were also noted. The results of the blood cell count and hepatic and renal function tests were normal. Serum levels of C-reactive protein and complements (C3, C4, CH50) were also normal. Serological examinations showed increased anti-DNA antibody (14 U/ml, [normal, < 6]). Antinuclear antibody was positive at a titer of 1:1380. CSF study showed an increased protein concentration of 83 mg/dl and an IgG level of 14 mg/dl with a normal number of cells. MR images revealed a T1-low, T2-high signal lesion at the upper part of the left ventral medulla. MR images of the brain and spinal cord were normal. The patient was diagnosed as having SLE. High-dose intravenous methylprednisolone (1 g/day) pulse treatment that was started 25 days after the onset of neurological symptoms, produced partial relief. Our case presented with paraplegia with a focal lesion in the left upper ventral part of the medulla on MR images. The incidence of male SLE is low, and paraplegia is a rare complication of SLE. Thus, the medullary lesion in SLE observed in our case appears to be rare. SLE should be considered as a cause of acute onset paraplegia or myelopathy.
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PMID:[A man with systemic lupus erythematosus presenting with spastic paraplegia]. 936 89

The objective was to study the relationship between the levels of interleukin-1 receptor antagonist (IL-1Ra) and disease activity and the acute-phase response in SLE patients with and without renal involvement. Twenty SLE patients who had distinct active clinical manifestations (eight glomerulonephritis, four systemic vasculitis without kidney involvement, nine skin rash, 12 arthritis, five serositis, four neuropsychiatric manifestations, three thrombocytopenia, one myositis and one haemolytic anaemia) were studied during a period of 8-12 months. Serum and plasma samples were taken at intervals of 6 weeks-4 months and tested for IL-1Ra, IL-1 beta, IL-6, IgG and anti-dsDNA, Clq, C3, C4 and C-reactive protein (CRP). IL-1Ra serum concentrations were increased in most SLE patients with active disease when compared to normal blood donors. However, at the time of flare, significantly higher levels of IL-1Ra were observed in patients with extra-renal disease as compared to other patients (median [range]: 363 [202-3041] and 4847 [268-27180] pg/ml for patients with and without renal involvement, respectively). This difference was not due to proteinuria. IL-1Ra levels did not correlate with SLEDAI score during flares, but they were elevated during flares in patients with extra-renal manifestations. When disease activity was at its highest, IL-1Ra concentrations correlated with IL-1 beta (r = 0.76; P < 0.001), IL-6 (r = 0.60; P < 0.01) and CRP (r = 0.61; P < 0.01), but not with C1q, C3, C4 and anti-dsDNA levels. The study showed that the pattern of inflammatory cytokines in active SLE varies in a manner that is dependent on which organs are involved. A relative absence of IL-1Ra response appears to be a feature characteristic of kidney involvement. IL-1Ra elevation clearly correlates with flares involving other organs.
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PMID:Low levels of interleukin-1 receptor antagonist coincide with kidney involvement in systemic lupus erythematosus. 944 89


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