| 1. |
- Jönsen, Andreas, et al.
(författare)
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Analysis of HLA DR, HLA DQ, C4A, FcgammaRIIa, FcgammaRIIIa, MBL, and IL-1Ra allelic variants in Caucasian systemic lupus erythematosus patients suggests an effect of the combined FcgammaRIIa R/R and IL-1Ra 2/2 genotypes on disease susceptibility.
- 2004
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1465-9905. ; 6:6, s. 557-562
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Tidskriftsartikel (refereegranskat)abstract
- Dysfunction in various parts of immune defence, such as immune response, immune complex clearance, and inflammation, has an impact on pathogenesis in systemic lupus erythematosus (SLE). We hypothesised that combinations of common variants of genes involved in these immune functions are associated with susceptibility to SLE. The following variants were analysed: HLA DR3, HLA DQ2, C4AQ0, Fcgamma receptor IIa (FcgammaRIIa) genotype R/R, Fcgamma receptor IIIa (FcRgammaIIIa) genotype F/F, mannan-binding lectin (MBL) genotype conferring a low serum concentration of MBL (MBL-low), and interleukin-1 receptor antagonist (IL-1Ra) genotype 2/2. Polymorphisms were analysed in 143 Caucasian patients with SLE and 200 healthy controls. HLA DR3 in SLE patients was in 90% part of the haplotype HLA DR3-DQ2-C4AQ0, which was strongly associated with SLE (odds ratio [OR] 2.8, 95% CI 1.7-4.5). Analysis of combinations of gene variants revealed that the strong association with SLE for HLA DR3-DQ2-C4AQ0 remained after combination with FcgammaRIIa R/R, FcgammaRIIIa F/F, and MBL-low (OR>2). Furthermore, the combination of the FcgammaRIIa R/R and IL-1Ra 2/2 genotypes yielded a strong correlation with SLE (OR 11.8, 95% CI 1.5-95.4). This study demonstrates that certain combinations of gene variants may increase susceptibility to SLE, suggesting this approach for future studies. It also confirms earlier findings regarding the HLA DR3-DQ2- C4AQ0 haplotype.
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| 2. |
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| 3. |
- Jönsen, Andreas, et al.
(författare)
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The heterogeneity of neuropsychiatric systemic lupus erythematosus isreflected in lack of association with cerebrospinal fluid cytokineprofiles
- 2003
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 12:11, s. 846-850
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to study the occurrence of autoantibodies and cytokines in serum and cerebrospinal fluid (CSF) in neuropsychiatric systemic lupus erythematosus (NPSLE). In total, 28 consecutive patients with NPSLE and 16 systemic lupus erythematosus (SLE) patients without neuropsychiatric involvement (non-NPSLE) were studied. IFN-alpha, IL-6, IL-10, soluble terminal complement complex (TCC), anti-ribosomal P protein antibodies (anti-P) and anti-cardiolipin antibodies (aCL) were measured in serum and CSF by immunoassays. Analyses of white blood cell differential count, CSF-albumin/serum-albumin ratio, IgG-index in CSF and isoelectric focusing in serum and CSF were also performed. CSF specimens from 23 healthy individuals were used as controls. IFN-alpha was elevated in the CSF of 5 of 28 NPSLE patients compared to three of 14 among the non-NPSLE patients. IL-6 was elevated in CSF in three of 26 NPSLE patients. Normal concentration of IL-10 was found in CSF in all 27 NPSLE-patients analysed. IFN-alpha in serum was elevated in 18 of 28 NPSLE patients. No distinct clinical phenotype was related to elevated cytokine concentration in serum or CSF. One patient with cerebral involvement complicated by progressive multifocal leukoencephalopathy displayed a very high IFN-alpha concentration in serum. High concentration of TCC was present in CSF from only one patient with systemic vasculitis and focal cerebral symptoms. In conclusion, the results of this study suggest that the diagnostic value of serum and CSF concentrations of IFN-alpha, IL-10, IL-6 and TCC is limited in unselected neuropsychiatric SLE, probably due to the heterogeneity of NPSLE pathogenesis.
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| 4. |
- Nived, Ola, et al.
(författare)
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High predictive value of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for survival in systemic lupus erythematosus.
- 2002
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 29:7, s. 1398-1400
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We previously reported high Systemic Lupus International Collaborating Clinics (SLICC) scores in fatal cases of systemic lupus erythematosus (SLE) from our inception cohort. This study was done to clarify if the SLICC damage scores 5 years after diagnosis predicted the outcome. METHODS: We studied 80 patients with SLE (70 women, 10 men), all enrolled and diagnosed during the years 1981 through 1991 in our inception cohort, and all alive 5 years after inclusion into the cohort. In all patients the SLICC/American College of Rheumatology (ACR) damage index (DI) was scored at 5 years after SLE diagnosis, and these scores were tested for predictive value. The outcomes were survival or late mortality within the following median observation period of 7 years. All surviving patients were followed through 1999, and no patient was lost to followup. RESULTS: At study entry, 5 years after the diagnosis of SLE, 37 patients had no damage to score with SLICC. Of the remaining 43 patients, 25 had a score of 1 and 18 had a score of 2 or more. In total, 14 fatalities occurred within 7 years after study entry, 7 among the 18 with initial SLICC/ACR DI of 2 or more compared with 7 fatalities among the 62 with less or no damage (p < 0.01). Cardiovascular or cerebrovascular SLICC/ACR DI items were more common in fatal cases than in survivors (p < 0.001). A SLICC score at 5 years of 2 or more increased the relative risk for fatality by 3.4 (95% CI 1.5-14.4), and had a predictive value of 38%. A SLICC score of 0 at 5 years gave an odds ratio in favor of survival of 0.06 (95% CI 0.0-0.5) and had a predictive value for survival of 97%. During an extended followup for one more year the predictive value of damage for fatalities was even more pronounced (p = 0.003, log-rank). CONCLUSION: SLICC damage scores registered 5 years after SLE diagnosis have a high predictive value for survival during the following median observation time of 7 years. These data provide strong evidence that the items included in the SLICC score are clinically relevant.
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| 5. |
- Shoenfeld, Yehuda, et al.
(författare)
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Features associated with epilepsy in the antiphospholipid syndrome
- 2004
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 31:7, s. 1344-1348
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the frequency of epilepsy in primary and secondary antiphospholipid syndrome (APS); to analyze the clinical and laboratory features characterizing those with epilepsy in a cohort of 538 patients with APS; and to find associated features that would suggest risk factors for epilepsy in APS. METHODS: We analyzed the clinical features of patients with APS who had epilepsy and compared them to the clinical features of non-epileptic APS patients. RESULTS: Of 538 APS patients, 46 (8.6%) had epilepsy. Epilepsy was more prevalent among APS secondary to systemic lupus erythematosus (SLE) compared to primary APS (13.7% vs 6%; p < 0.05). The patients with epilepsy had a higher prevalence of central nervous system (CNS) manifestations including focal ischemic events (strokes or transient ischemic events, 54.3% vs 24.6%; p < 0.0001) and amaurosis fugax (15.2% vs 4.9%; p < 0.05). APS patients with epilepsy had a higher frequency of valvular pathology (30.4% vs 14.6%; p < 0.01), thrombocytopenia (43.5% vs 25%; p < 0.05), and livedo reticularis (26.1% vs 11.5%; p < 0.01). The multivariate logistic regression analysis found CNS thromboembolic events as the most significant factor associated with epilepsy, with an odds ratio (OR) of 4.05 (95% confidence interval, CI: 2.05-8), followed by SLE (OR 1.4, 95% CI 1.2-4.7), and valvular vegetations (OR 2.87, 95% CI 1-8.27). CONCLUSION: Epilepsy is common in APS and most of the risk seems to be linked to vascular disease as manifested by extensive CNS involvement, valvulopathy, and livedo reticularis and to the presence of SLE. These factors, however, explain only part of the increased occurrence of epilepsy in APS and other causes such as direct immune interaction in the brain should be investigated.
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| 6. |
- Shoenfeld, Y, et al.
(författare)
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Prevalence and clinical correlations of antibodies against six beta 2-glycoprotein-I-related peptides in the antiphospholipid syndrome
- 2003
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Ingår i: Journal of Clinical Immunology. - 0271-9142. ; 23:5, s. 377-383
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Tidskriftsartikel (refereegranskat)abstract
- Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.
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| 7. |
- Ståhl Hallengren, Christina, et al.
(författare)
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Incidence studies of systemic lupus erythematosus in Southern Sweden: increasing age, decreasing frequency of renal manifestations and good prognosis
- 2000
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 27:3, s. 685-685
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify all new cases of systemic lupus erythematosus (SLE) within a defined area in Southern Sweden with validated methods of retrieval, and to compare 2 cohorts assembled during 1981-86 and 1987-91. METHODS: The catchment area, the health care district of Lund-Orup, had during 1981-91 a mean adult population (> 15 years of age) of 172,300 individuals. During 1987-91 we identified 379 individuals with potential SLE diagnosis from diagnosis registers and from central laboratory databases. Out of these, 121 had a previously known SLE diagnosis. All patient records were reviewed and patients with possible SLE not already known at the SLE unit were invited and examined. Organ damage was recorded as the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index. RESULTS: Forty-one new SLE cases were diagnosed during 1987-91, giving a median annual incidence of 4.8/100,000 inhabitants, with a median age at diagnosis of 47 years. The incidence is similar to that found 1981-86 (4.5/100,000/year) in the same population using the same methods for retrieval. Age and sex-specific incidence 1981-91 was notably highest at the age of 65-74 (14.1/100,000/year) in women and age 65-74 (3.2/100,000/year) in men. The point prevalence on December 31, 1986, was a 42/100,000 and on December 31, 1991, 68/100,000. The 5 year survival was 93% and 10 year survival 83%. While overall survival was not decreased, 10 year survival was slightly reduced compared with an age and sex matched healthy population (p = 0.03). In the 1987-91 cohort the sensitivity of the American Rheumatism Association criteria was 92.7% and the specificity was 94%. The frequency of renal manifestations was decreased in the latter cohort. The damage rate was highest during the first year and then constant during a 5 year followup, and was similar in the 2 cohorts. Damage that related to atherosclerosis was common and cardiovascular disease was the most common cause of death. CONCLUSION: The incidence of SLE in Sweden was notably constant during the 11 years 1981-91. Mortality was low and only late mortality (> 10 years disease duration) exceeded that in an age and sex matched control population. Atherosclerosis was the main cause of damage and mortality. Specificity and sensitivity of the ACR classification criteria are high in this epidemiologically recruited cohort.
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