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)

The aim of this study was to determine the distribution of the FcgammaRlla and FcgammaRIIIa polymorphisms and their association with clinical manifestations in Korean lupus patients. Three hundred SLE (systemic lupus erythematosus) patients (48 male, 252 female) meeting 1982 ACR criteria and 197 Korean disease-free controls were enrolled. Genotyping for FcgammaRlla 131 R/H and FcgammaRIIIa 176 F/V was performed by PCR of genomic DNA using allele-specific primers and the FcgammaRIIIa genotype was confirmed by direct sequencing of PCR product in some cases. There was significant skewing in the distribution of the three FcgammaRIIa genotypes between the SLE and the controls (P=0.002 for R/R131 vs R/H131 and H/H131, OR 2.5 (95% Cl 1.4-4.5), but not in FcgammaRIIIa genotypes. FcgammaRIIa-R allele was a significant predictor of lupus nephritis, as compared with SLE patients without nephritis (P=0.034 for R131 vs H131, OR 1.4 (95% Cl 1.03-1.9)), but proliferative nephritis (WHO class III and IV) was less common in patients with FcgammaRlla-R/R131 and in FcgammaRIIa-R allele. In 300 SLE patients, high binding allele combination H131/V176 was less common in SLE with nephritis than in SLE without nephritis. Hemolytic anemia was less common in R131/F176 allele combination among four FcgammaRIIa/FcgammaRIIIa allelic combinations. Male SLE patients showed a higher frequency of renal involvement, serositis, thrombocytopenia, malar rash and discoid rash than female SLE, and male SLE had a higher frequency of FcgammaRIIa-R/R131 or R131-allele than male controls, but FcgammaRIIa or FcgammaRIIIa genotypes had no association with renal involvement in male SLE patients. FcgammaRIIa-H/H131 showed a higher frequency of hemolytic anemia and less pulmonary complications in male SLE. Female SLE patients showed higher frequency of any hematologic abnormality, lymphopenia, anticardiolipin antibody (+) and anti-Ro antibody (+) than male SLE, and had earlier onset of first symptoms. There was no skewing in FcgammaRIIa or FcgammaRIIIa genotypes between female SLE and female controls, but FcgammaRIIa-R131 allele showed skewing between female SLE with nephritis and female SLE without nephritis. The age at onset of thrombocytopenia was earlier in FcgammaRIIa R/R131 among three FcgammaRIIa genotypes, and serositis in FcgammaRIIIa-F/F176 among three FcgammaRIIIa genotypes. FcgammaRIIa-R131 homozygote was a major predisposing factor to the development of SLE and FcgammaRIIa-RI31 homozygote and R131 allele were a predisposing factor, and H131/V176 was a protective allele combination in lupus nephritis. In contrast to other ethnic patients, in our study cohort, clinical manifestation was different between male and female, and FcgammaRIIa and FcgammaRIIIa showed somewhat different clinical associations between the genders.
Lupus 2001
PMID:FcgammaRIIa/IIIa polymorphism and its association with clinical manifestations in Korean lupus patients. 1148 Aug 43

The objective of this study was to retrospectively explore the safety and efficacy of leflunomide (LEF) in outpatients with systemic lupus erythematosus (SLE). Eighteen SLE females received LEF, open label, 100 mg/day loading dose for 3 days followed by 20 mg per day. Patients were evaluated for safety and efficacy after 2-3 months of therapy. The mean age was 42.6 y and mean disease duration 7.9 y. ACR criteria were met by 15/18. Four patients stopped LEF during the observation period. Ten of 14 LEF-treated patients had subjective improvement with 9/14 patients achieving lower SLEDAI scores. The mean SLEDAI decreased by 2.1 (P=0.005) and the mean ESR decreased by 9mm/h (P=0.02). Prednisone dosages could be reduced in 2/5 subjects without a flare. No organ-threatening or life-threatening side effects were seen in our patients. Diarrhea occurred in seven patients (two stopped LEF), rash occurred in one patient (stopped LEF), one patient stopped LEF for reasons not related to therapy. Blood pressure was unchanged. Leflunomide was efficacious and safe in this cohort of SLE patients after 2-3 months of therapy. Placebo-controlled trials of longer duration are indicated.
Lupus 2001
PMID:Benefits of leflunomide in systemic lupus erythematosus: a pilot observational study. 1148 Aug 45

This study describes the importance of mannose-binding lectin (MBL) variant alleles for systemic lupus erythematosus (SLE) and accompanying infections in a population-based cohort. MBL alleles were determined in 99 SLE patients recruited from a representative Danish region. Patients were classified according to the 1982 revised ACR criteria as definite SLE (D-SLE) (n = 77) fulfilling > or =4 criteria and incomplete SLE (I-SLE) (n = 22) with 0.99, respectively). A meta-analysis of eight previously published studies suggested that the presence of MBL variant alleles confer a 1.6 times overall increased risk for D-SLE (P < 0.00001). MBL variant allele carriers had higher disease activity (SLEDAI-index) in a 2-year follow-up period (P = 0.02) and had an increased risk of acquiring complicating infections in general (P = 0.03) and respiratory infections in particular (P = 0.0006). Only in SLE patients fulfilling > or =4 ACR criteria an increased frequency of MBL variant alleles was found. MBL variant alleles were also associated with increased risk of disease activity and of complicating infections indicating that the MBL gene is an SLE disease modifier locus.
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PMID:Association of mannose-binding lectin gene variation with disease severity and infections in a population-based cohort of systemic lupus erythematosus patients. 1178 11

Estrogen metabolism in women with SLE is weighted towards 16alpha-hydroxyestrone, an estrogenic compound that might fuel disease activity. Indole-3-carbinol (I3C) is a nutritional compound that can shift estrogen metabolism towards less estrogenic metabolites. However, the effects of I3C in women with SLE have not been studied. Open-label 1-week metabolic study of 375 mg/day I3C was carried out in women with SLE, followed by a 3-month observational period for disease activity. The primary outcome measure was the change in ratio of urinary 2:16alpha hydroxyestrone levels. Secondary measures included the SLE Disease Activity Index. Seventeen clinically premenopausal women fulfilling ACR criteria for probable/definite SLE (mean age 37.9 y, range 20-49 y, mean disease duration 4.3 y, range 0.5-15) completed the 1-week metabolic study; 12 took I3C for 3 months. The mean 2:16alpha hydroxyestrone ratio increased by 1.84 to 3.15 (P = 0.0001). Mean SLEDAI scores were 10.0 (baseline); 6.25 (3 months); and 8.8 (3 months after withdrawal; P = NS). Women with SLE can manifest a metabolic response to I3C and might benefit from its antiestrogenic effects. We did not observe any striking effects on SLE disease activity during the 3-month observational period.
Lupus 2001
PMID:Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity. 1178 85

The aim of the present study was to assess the effects of disease severity and demonstrable organ damage as risk factors for the development of osteoporosis in systemic lupus erythematosus (SLE). Sixty-four SLE patients were included. Mean disease duration was 7.7 +/- 5.7 y. Thirty-two patients had persistent organ damage, defined as SLICC-ACR damage score > or = 1. Disease activity measured by SLAM-2 ranged from 3 to 27. Bone mineral density (BMD) measurements were performed with dual X-ray absorptiometry. In addition, biochemical markers of bone metabolism were studied. BMD was inversely correlated with disease duration, damage score and cumulative glucocorticoid intake, but no correlation was found for current glucocortioid use or with markers of bone metabolism. In a multivariate analysis, body weight, disease duration and damage index fitted best for the prediction of BMD at both lumbar spine and femoral neck. Seven out of 64 patients had osteoporosis according to WHO criteria. In conclusion, severe osteoporosis is uncommon in lupus patients. Disease activity and severity were no major risk factors for loss of BMD in this study, but persistent non-bone-related organ damage was significantly linked to the presence of osteoporosis measured as decreased BMD. Our data suggest that, in addition to patients receiving glucocorticoids, patients with an SLICC-ACR > or = 1 or a disease duration > or = 7 y might benefit from regular monitoring of BMD as secondary prevention of damage.
Lupus 2001
PMID:Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage. 1178 91

Despite the prognostic importance of learned helplessness (LH) in rheumatic diseases, there are no validated measures of LH in Chinese or other Asian languages. We therefore assessed the validity of a Chinese translation of the Rheumatology Attitudes Index (CRAI; a widely used measure of LH) and its Helplessness (CHS) and Internality (CIS) subscales in patients with SLE. Chinese-speaking SLE patients (n = 69) completed identical, self-administered questionnaires containing the CRAI and assessing demographic/socio-economic variables twice within 2 weeks. SLE activity, damage and quality of life were assessed using the BILAG, SLICC/ACR Damage Index and SF-36 respectively. Scale psychometric properties were assessed through Cronbach's alpha, intra-class correlations, quantifying test-retest differences, factor analysis and known-groups construct validity. Internal consistency and reliability were acceptable, with Cronbach's alpha for the CHS, CIS and CRAI being 0.70, 0.69 and 0.74, respectively. Mean differences in test-retest scores spanned 1.6-2.4% of possible scale ranges and intra class correlations ranged from 0.72 to 0.88. Factor analysis identified two major factors corresponding to the CHS and CIS subscales of the CRAI. Eight of 10 a priori hypotheses relating the CRAI and CHS to demographic, disease and quality of life variables were confirmed, supporting the construct validity of these scales. The CRAI and its helplessness subscale are valid and reliable measures of learned helplessness in Chinese-speaking SLE patients.
Lupus 2002
PMID:A Chinese version of the Rheumatology Attitudes Index is a valid and reliable measure of learned helplessness in patients with SLE. 1195 83

Systemic lupus erythematosus (SLE) is an inflammatory multisystem disease of unknown etiology with immunologic aberrations. Many studies have shown that genetic and environmental factors are implicated in the development of SLE. Angiotensin-converting enzyme (ACE) affects various immune phenomena through the renin-angiotensin and kallikrein-kininogen systems by creating angiotensin II and inactivating bradykinin. We investigated the correlation between insertion/ deletion polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement and lupus nephritis. Two-hundred and eleven Korean patients fulfilling the ACR criteria and 114 healthy subjects were enrolled. The ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. The nephritis patients were classified by the WHO classification. In addition, the activity and chronicity index were used to assess the severity of renal involvement. We evaluated vascular involvement by the presence or absence of hypertension, Raynaud's phenomenon, livedo reticularis, antineutrophil cytoplasmic antibody and the SLICC/ACR Damage Index. The gene frequency of ACE gene polymorphism was as follows: II 39 vs 34%, ID 41 vs 50%, DD 20 vs 16% in SLE patients and controls, respectively. There was no difference in genotype frequency between both groups. There were no significant differences between the distribution of ACE gene genotypes and lupus nephritis and its related parameters, including WHO classification, activity index, chronicity index, renal dysfunction and amount of 24 h urinary protein. The ACE genotypes and alleles did not affect the presence of vascular manifestations evaluated, but the frequency of DD genotype was significantly low in SLE patients with Raynaud's phenomenon compared to those without Raynaud's phenomenon (P = 0.002 for ACE ID vs DD and II, OR 2.7, 95% CI 1.43-5.09; P=0.023 for ACE DD vs ID and II, OR 0.33, 95% CI 0.12-0.89). Also skewing from DD to II genotype was noted in patients with anti-Sm antibody compared to those without anti-Sm antibody (P = 0.025 for ACE DD vs ID and II, OR 0.21, 95% CI 0.05-0.93). The onset age of serositis was older in patients with the ID genotype than the others (ID= 34.5+/-10.8, II + DD = 25.6+/-10.2, P= 0.002). Also the onset age of malar rash was older in patients with II genotype than the others (II=26.7+/-8.4, ID+DD=21.3+/-9.0; P=0.021). The patients with I allele showed a significantly higher frequency of serositis (P = 0.022). Taken together, the I/D polymorphisms of ACE gene did not affect susceptibility of SLE, lupus nephritis and the vascular manifestations, including Raynaud's phenomenon, in Korean SLE patients, although the DD genotype was negatively associated with Raynaud's phenomenon among SLE patients. However, it would be valuable to evaluate the role of other genes potentially related to vascular events, such as endothelin, nitric oxide or angiotensin II receptor as well as ACE gene.
Lupus 2002
PMID:Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE. 1263 Jul 62

Systemic lupus erythematosus-associated irreversible organ/system damage was previously associated with various clinical and demographic features. We analysed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) in a cohort of 151 Israeli patients followed for a mean (+/- s.d.) period of 45.7 +/- 37.4 months. Mean score of SLICC/ACR DI at the first and last encounters were 0.17 +/- 64 and 1.64 +/- 2.1, respectively (P < 0.0001). Multiple logistic regression analyses disclosed a statistically significant positive correlation with corticosteroid and cyclophosphamide therapy. Hydroxychloroquine therapy was significantly associated with lower SLICC/ACR DI. Although the size of our study group did not allow us to find specific organs/systems which were associated with the protective effect of hydroxychloroquine, we suggest this is due to the antiatherogenic effects attributed to antimalarial therapy in SLE.
Lupus 2002
PMID:Protective effect of hydroxychloroquine in systemic lupus erythematosus. Prospective long-term study of an Israeli cohort. 1213 73

The etiological role of hair dye treatment (HDT), some of them such as permanent hair dyes containing aromatic amines, in the development of SLE has been previously ruled out. However, the possible influence of HDT use on the course and prognosis of lupus patients has been assessed only in one short-term study. Since HDT is very extensive among the population, the knowledge of this possible negative effect may be very important. Thus, the aim of this study was to assess the long-term influence of several HDTs on the course and clinical severity of patients with both systemic lupus erythematosus (SLE) and cutaneous lupus (CL). In this longitudinal case series study, 91 SLE patients and 22 CL patients were prospectively studied from October 1988 to May 2000. They were divided into three groups: (a) non-HDT users--patients who have never used HDT (n = 65); (b) P-HDT users--HDT permanent type users, alone or in combination with other types of HDT (n = 28); (c) non P-HDT--users of other treatments different from permanent tinting (bleach, lowlights, etc; n = 20). In each patient we determined: (1) number of flares/year in SLE patients and worsening of cutaneous lesions for CL; (2) Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index; (3) predominant damaged organs/systems according to the HDT use and type of HDT; and (4) subjective impression about the disease evolution in relation to HDT use. No significant differences were found with respect to flares/year and SLICC/ACR damage index between the study groups. Non-HDT group presented more renal involvement and serositis than both HDT-user groups. No patient related the HDT use to the worsening of his disease. Therefore, in this study no evidence of an association between the long-term use of several types of HDT and the clinical activity and course of SLE and CL was found.
Lupus 2002
PMID:Hair dye treatment use and clinical course in patients with systemic lupus erythematosus and cutaneous lupus. 1219 84

The aim of this open study was to compare the outcomes and side effects of plasmapheresis (PP) in patients with proliferative lupus nephritis treated with cyclophosphamide (Cyc) boluses. The study involved 28 consecutive patients. All of the patients met the ACR modified criteria for SLE and underwent a qualifying renal biopsy. In group I, patients were treated with synchronised therapy (PP, 50 ml/kg, followed by pulse Cyc, 750 mg/m(2), repeated monthly for 6 months), whereas in group II, they were given only intermittent Cyc boluses (at the same dosage). The data were collected in the patients' records according to a standardised protocol. Patients were followed-up for a mean of 4 years. The disease-free survival was analysed using Kaplan-Meier estimated survival curves ([S(t)]). At the end of the 6-month treatment period, a statistically significant number of patients in group I (75%) was in complete remission in comparison to group II (31%) (P < 0.02), whereas at long-term follow-up, these percentages were similar (41% vs. 50%, P = n.s.). The main functional and immunological parameters showed a normalisation in both groups. The risk of a poor renal outcome significantly correlated with high serum creatinine levels at the onset of nephritis (P < 0.05). We documented a higher rate of infectious complications in group I. This study reports that synchronised therapy is useful in inducing a faster remission in patients with proliferative lupus nephritis. However, it is not superior to conventional therapy at long term follow-up analysis. Positive results should be reinforced by a long-term maintenance therapy.
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PMID:Synchronised therapy and high-dose cyclophosphamide in proliferative lupus nephritis. 1221 Jul 9


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