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- Alizadeh, Behrooz Z, et al.
(författare)
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Functional Variants of Fc Gamma Receptor (FCGR2A) and FCGR3A Are Not Associated with Susceptibility to Systemic Sclerosis in a Large European Study (EUSTAR).
- 2010
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; Jul 1, s. 1673-1679
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the possible role of FCGR2A 519A>G and FCGR3A 559A>C functional polymorphisms in the genetic predisposition to susceptibility to systemic sclerosis (SSc) or clinical phenotype. METHODS: A total of 1566 patients with SSc and 2271 geographically matched controls were included in our study. We analyzed the genotype and allele frequencies of the FCGR2A 519A>G and FCGR3A 559A>C functional variants in 6 independent European cohorts of white patients with SSc, and white controls. The cohorts comprised 165 Dutch patients with SSc and 1326 controls, 236 Spanish patients with SSc and 257 controls, 267 German patients with SSc and 270 controls, 202 Swedish patients with SSc and 261 controls, 416 Italian patients with SSc and 157 controls, and additionally 280 English patients with SSc. Genotyping was performed using Taqman 5' allelic discrimination assay. The study reached a 99% power to detect the effect of a polymorphism at an OR of 1.3. RESULTS: Neither FCGR2A 519A>G nor FCGR3A 559A>C was significantly associated with susceptibility to SSc. We did not find an association with specific disease phenotypes, limited or diffuse cutaneous involvement, autoantibody profiles, or pulmonary involvement. CONCLUSION: Our study strongly suggests the lack of a role for the FCGR2A 519A>G and FCGR3A 559A>C polymorphisms in SSc susceptibility or clinical phenotype in 6 independent European cohorts.
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| 2. |
- Andréasson, Kristofer, et al.
(författare)
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Mycophenolate mofetil for systemic sclerosis : drug exposure exhibits considerable inter-individual variation-a prospective, observational study
- 2020
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Ingår i: Arthritis Research & Therapy. - : BMC. - 1478-6362 .- 1478-6354. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Mycophenolate mofetil (MMF) is an established therapy for systemic sclerosis (SSc), but its pharmacokinetics in this disease remains unexplored. We have investigated drug exposure in MMF-treated patients with SSc in relation to clinical features of the disease and common concomitant drugs.Methods: This study was predefined to include 35 MMF-treated SSc patients who were using MMF at a fixed dose of 0.5, 1.0 or 1.5g twice daily since at least 3months. The 12-h drug exposure of the active MMF metabolite mycophenolic acid (MPA) was estimated by repeated analysis of plasma MPA over a 6-h period. This 12-h drug exposure was dose normalised to a daily intake of 3g MMF (MPA_AUC(3g)) in order to compare subjects using MMF at different doses. Drug exposure was analysed in reference to the clinical characteristics including body weight, renal function, autoantibodies, intestinal dysbiosis, intestinal inflammation assessed by faecal (F)-calprotectin, intestinal symptoms assessed by the University of California Los Angeles Scleroderma Trial Consortium Gastrointestinal Tract Instrument 2.0 and concomitant drug usage including proton-pump inhibitors (PPI).Results:Thirty-four out of 35 study participants completed the study. The mean daily MMF dose was 2.1g. Drug exposure expressed as MPA_AUC(3g) varied up to 8-fold between patients (median 115, range 27-226mg h/L).MPA_AUC(3g) was inversely related to body weight (r(s)=-0.58, p<0.001) and renal function (r(s)=-0.34, p=0.054). Anti-topoisomerase-1 antibodies and male sex were associated with lower MPA_AUC(3g) (87 vs 123 and 71 vs 141; p=0.008 and p=0.015, respectively). MPA_AUC(3g) was inversely related to the intestinal abundance of lactobacilli and to F-calprotectin (r(s)=-0.54, p=0.004; r(s)=-0.36, p=0.034), but not to gastrointestinal symptoms. MPA_AUC(3g) was inversely related to PPI usage (r(s)=-0.45, p=0.007). We found no association between MPA_AUC(3g) and disease subtype, disease duration or disease activity.Conclusion: MMF-treated SSc patients exhibit considerable inter-individual variation in drug exposure, and lower MPA levels were primarily found in PPI users with poor prognostic factors. Body weight, renal function, sex, serology, gastrointestinal manifestations and/or measuring individual MPA exposure should be considered when using MMF for SSc.
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| 3. |
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| 4. |
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| 5. |
- Aronsson, David, et al.
(författare)
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Airway resistance and reactance are affected in systemic sclerosis.
- 2015
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Ingår i: European clinical respiratory journal. - : Informa UK Limited. - 2001-8525. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Interstitial lung disease often occurs as an early complication of systemic sclerosis (SSc). The aim was to investigate whether impulse oscillometry (IOS) could be used to evaluate lung impairment in SSc.
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| 6. |
- Bengtsson, Anders A., et al.
(författare)
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Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren’s Syndrome and Systemic Sclerosis
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diag- nose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway.
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| 7. |
- Broen, Jasper C A, et al.
(författare)
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The Functional Polymorphism 844 A>G in Fc{alpha}RI (CD89) Does Not Contribute to Systemic Sclerosis or Rheumatoid Arthritis Susceptibility.
- 2011
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 38:3, s. 446-449
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the role of the Fc(α)RI 844 A>G functional polymorphism in the genetic predisposition to rheumatoid arthritis (RA) and systemic sclerosis (SSc) susceptibility. METHODS: The study population was composed of 1401 patients with SSc, 642 patients with RA, and 1317 healthy controls. The Fc(α)RI (CD89) single-nucleotide polymorphism rs16986050 was genotyped by pyrosequencing. RESULTS: We observed no significant deviation of the genotype and allele frequencies in RA and SSc compared to controls. A metaanalysis and a recessive and dominant model yielded similar negative results. CONCLUSION: Our data show that the Fc(α)RI 844 A>G polymorphism is not associated with SSc or RA susceptibility.
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| 8. |
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| 9. |
- Carlsson, Anders, et al.
(författare)
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Serum protein profiling of systemic lupus erythematosus and systemic sclerosis using recombinant antibody microarrays.
- 2011
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Ingår i: Molecular & Cellular Proteomics. - 1535-9484. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two severe autoimmune connective tissue diseases. The fundamental knowledge about their aetiology is limited and the conditions display complex pathogenesis, multifaceted presentations, and unpredictable courses. Despite significant efforts, the lack of fully validated biomarkers enabling diagnosis, classification, and monitoring of disease activity represents significant unmet clinical needs. In this discovery study, we have for the first time used recombinant antibody microarrays for miniaturized, multiplexed serum protein profiling of SLE and SSc, targeting mainly immunoregulatory proteins. The data showed that several candidate SLE-associated multiplexed serum biomarker signatures were delineated, reflecting disease (diagnosis), disease severity (phenotypic subsets) and disease activity. Selected differentially expressed markers were validated using orthogonal assays and a second, independent patient cohort. Further, biomarker signatures differentiating SLE versus SSc were demonstrated, and the observed differences increased with severity of SLE. In contrast, the data showed that the serum profiles of SSc versus healthy controls were more similar. Hence, we have shown that affinity proteomics could be used to de-convolute crude, non-fractionated serum proteomes, extracting molecular portraits of SLE and SSc, further enhancing our fundamental understanding of these complex autoimmune conditions.
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| 10. |
- Chaplin, John, et al.
(författare)
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Varför ska du använda PROMIS? : Nytt system för patientrapporterad utfallsmått
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- PROMIS är ett itembanksystem för hälso- och sjukvården. Syftet är att erbjuda moderna, patientrapporterade mått som kan användas för flertalet patientgrupper till en mycket låg kostnad och med ett nationellt supportsystem.En itembankär en modern form av elektronisk enkät som kan innehålla ett stort antal enkätfrågor. Ett datorprogram väljer ut de mest lämpade frågorna till varje person utifrån dennes svar på föregående frågor, på så sätt enkäten individanpassas.
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