| 1. |
- Foltyn Zadura, Anna, et al.
(författare)
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Factor H autoantibodies and deletion of Complement Factor H-Related protein-1 in rheumatic diseases in comparison to atypical hemolytic uremic syndrome.
- 2012
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Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: INTRODUCTION: Complement activation is involved in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and atypical hemolytic uremic syndrome (aHUS). Autoantibodies to complement inhibitor factor H (FH), particularly in association with deletions of the gene coding for FH-related protein 1 (CFHR1), are associated with aHUS. METHODS: Autoantibodies against FH, factor I (FI) and C4b-binding protein (C4BP) were measured by ELISA, while CFHR1 homozygous deletion was determined with Western blotting of sera. Epitopes for FH autoantibodies were mapped using recombinant fragments of FH. RESULTS: FH autoantibodies were detected in SLE (6.7%, n = 60, RA patients (16.5%, n = 97 in the Swedish cohort and 9.2%, n = 217 in the Dutch cohort) and thrombosis patients positive for the lupus anticoagulants (LA+) test (9.4%, n = 64) compared with aHUS patients (11.7%, n = 103). In the control groups (n = 354), an average of 4% of individuals were positive for FH autoantibodies. The frequencies observed in both RA cohorts and LA+ patients were statistically significantly higher than in controls. We also found that an average of 15.2% of the FH-autoantibody positive individuals in all studied disease groups had homozygous deficiency of CFHR1 compared with 3.8% of the FH autoantibody negative patients. The levels of FH autoantibodies varied in individual patients over time. FH autoantibodies found in LA+, SLE and RA were directed against several epitopes across FH in contrast to those found in aHUS, which bound mainly to the C-terminus. Autoantibodies against FI and C4BP were detected in some patients and controls but they were not associated with any of the diseases analyzed in this study. CONCLUSIONS: Autoantibodies against FH are not specific for aHUS but are present at a significant frequency in rheumatic diseases where they could be involved in pathophysiological mechanisms.
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| 2. |
- Abelson, Anna-Karin, et al.
(författare)
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No evidence of association between genetic variants of the PDCD1 ligands and SLE
- 2007
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:1, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
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| 3. |
- Bengtsson, Christine, et al.
(författare)
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Systemic lupus erythematosus and cardiac risk factors : medical record documentation and patient adherence
- 2011
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Ingår i: Lupus. - Houndmills, Basingstoke, Hampshire : Stockton. - 0961-2033 .- 1477-0962. ; 20:10, s. 1057-1062
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Tidskriftsartikel (refereegranskat)abstract
- This study explores patients' knowledge of cardiac risk factors (CRFs), analyses how information and advice about CRFs are documented in clinical practice, and assesses patient adherence to received instructions to decrease CRFs. Systemic lupus erythematosus (SLE) patients with >= 4 ACR criteria participated through completing a validated cardiovascular health questionnaire (CHQ). Kappa statistics were used to compare medical records with the self-reported CHQ (agreement) and to evaluate adherence. Two hundred and eleven (72%) of the known patients with SLE participated. The mean age of the patients was 55 years. More than 70% of the SLE patients considered hypertension, obesity, smoking and hypercholesterolaemia to be very important CRFs. The agreement between medical record documentation and patients' reports was moderate for hypertension, overweight and hypercholesterolaemia (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). Patients' self-reported adherence to advice they had received regarding medication was substantial to perfect (kappa 0.65-1.0). For lifestyle changes in patients with hypertension and overweight, adherence was only fair to moderate (kappa 0.13-0.47). Swedish SLE patients' awareness of traditional CRFs was good in this study. However, the agreement between patients' self-reports and medical record documentation of CRF profiles, and patients' adherence to medical advice to CRF profiles, could be improved. Lupus (2011) 20, 1057-1062.
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| 4. |
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| 5. |
- Compagno, Michele, et al.
(författare)
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Low diagnostic and predictive value of anti-dsDNA antibodies in unselected patients with recent onset of rheumatic symptoms: results from a long-term follow-up Scandinavian multicentre study.
- 2013
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 42:4, s. 311-316
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To verify the diagnostic accuracy of anti-double-stranded DNA (anti-dsDNA) antibodies detected by the Crithidia luciliae immunofluorescence test (CLIFT) in a cohort of unselected patients, referred to a rheumatologist due to recent onset of rheumatic symptoms. Method: A total of 1073 consecutive patients were screened for anti-nuclear antibodies (ANAs). Serum samples from 292 ANA-positive and 292 matching ANA-negative patients were tested three times for anti-dsDNA antibodies, using two different CLIFT kits (ImmunoConcepts(®) and Euroimmun(®)). An initial clinical diagnosis was made by rheumatologists unaware of the results. The diagnoses were updated after a median follow-up of 4.8 years. Results: CLIFT was positive at least once in 60 patients but only 23 patients were CLIFT positive in all of the assays. Diagnosis of systemic lupus erythematosus (SLE) was made initially in 65 patients, of whom 24 (37%) were CLIFT positive. Many other diagnoses were observed among the CLIFT-positive patients. Overall, 16 (5.5%) ANA-negative patients were CLIFT positive. After approximately 5 years, the diagnosis of SLE remained unchanged in 63 patients (23 CLIFT positive) and altered in only two (one CLIFT positive). Among the 36 CLIFT-positive patients who were not diagnosed with SLE at study entry, only one developed SLE during the follow-up period. Conclusions: CLIFT was not reliable as a diagnostic tool in unselected patients with rheumatic symptoms. ANAs were of little value as a screening test before the CLIFT analysis. CLIFT had surprisingly low positive predictive value (PPV) for the diagnosis of SLE despite its high specificity. For non-SLE patients, being CLIFT positive poses little risk of developing SLE within 5 years.
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| 6. |
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| 7. |
- Ekman, Carl, et al.
(författare)
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Plasma concentrations of Gas6 and sAxl correlate with disease activity in systemic lupus erythematosus.
- 2011
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 1064-1069
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. SLE is a systemic autoimmune disease with an annual incidence of 3.8 per 100 000. Several pathogenic mechanisms are believed to be operating in SLE, including an impaired clearance of apoptotic cells, activation of the type I IFN pathway and generation of autoimmune leucocytes. Growth arrest-specific protein 6 (Gas6) and its receptor Axl are known to regulate inflammation and may be implicated in lupus pathogenesis. We have recently developed immunological methods to quantify the vitamin-K-dependent protein Gas6 and its soluble receptor sAxl in human plasma, which we have used to investigate the role of Gas6 and soluble Axl in SLE. Methods. We have investigated the relation between the plasma concentrations of Gas6 and sAxl and disease activity and specific symptoms in 96 SLE patients. Results. Gas6 and sAxl concentrations correlated with SLEDAI (r = 0.48, P < 0.001 and r = 0.39, P < 0.001, respectively). Furthermore, concentrations of Gas6 and sAxl correlated with ESR and CRP and inversely with haemoglobin levels. Gas6 and sAxl concentrations were significantly higher in patients with anti-DNA antibodies, leucopenia and GN. Conclusion. The plasma concentrations of Gas6 and sAxl vary with disease activity in SLE, in particular GN, and may have a role in lupus pathogenesis. Furthermore, Gas6 and sAxl may be of use as biomarkers of disease activity.
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| 8. |
- Gateva, Vesela, et al.
(författare)
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A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:11, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
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| 9. |
- 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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| 10. |
- Jönsen, Andreas, et al.
(författare)
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Association between SLE nephritis and polymorphic variants of the CRP and Fc gamma RIIIa genes
- 2007
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 46:9, s. 1417-1421
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To study the relationship between clinical manifestations in systemic lupus erythematosus (SLE) with polymorphisms in suggested susceptibility genes encoding Fc gamma RIIa, Fc gamma RIIIa, Fc gamma RIIIb, CRP and IL-1Ra. Methods. Genetic polymorphisms were analysed in 323 unrelated SLE patients and 200 healthy blood donors. The genotype frequencies were compared between clinical subsets of SLE patients, as well as with healthy controls. Clinical manifestations included the ACR classification criteria. Nephritis was further classified according to WHO class on renal biopsy. Results. Presence of a CRP4 A-allele was associated with SLE nephritis (P< 0.01) and inversely correlated with arthritis (P < 0.01), when comparing within the SLE group. The Fc gamma RIIIa F/F genotype was also associated with nephritis (WHO class III and IV, P=0.04 for the SLE group) and in combination with the CRP4 A-allele a stronger association was noted (P<0.001). Furthermore, the Fc gamma RIIIb NA2/NA2 genotype was associated with butterfly rash (P< 0.01). An association was found between seizures and the presence of both the Fc gamma RIIa R/R and the Fc gamma RIIIa F/F genotypes (P< 0.01) and an inverse correlation between serositis and the CRP4 A-allele when present together with the IL-1Ra 2-allele (P=0.01). Furthermore, a combination of the Fc gamma RIIa R/R genotype and CRP4 A-allele was associated with lymphopenia (P= 0.02) and a similar result was found for the combination of Fc gamma RIIIa F/F and Fc gamma RIIIb NA2/NA2 (P= 0.04). Conclusions. Polymorphic variants of the CRP and Fc gamma-receptor genes are associated with the clinical phenotype in SLE. Our findings suggest an immune complex-mediated pathogenesis in nephritis and seizures, while development of arthritis may depend on other pathogenetic pathways.
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