| 1. |
- Alenius, Gerd-Marie, et al.
(författare)
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Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden
- 2002
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Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 21:5, s. 357-362
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility.
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| 2. |
- Allard, Karin, 1953-, et al.
(författare)
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The Education of Special Educators in Sweden and Finland
- 2017
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Konferensbidrag (refereegranskat)abstract
- Background: The educational policy is inclusive both in Finland and in Sweden. Still special educators are educated. They seem to work both in inclusive and in segregative ways. The more inclusive ways demand co-operation and planning with other teachers. Although the results of such co-operation have been good, there could be even more collaboration at schools. The main questions of our study are: 1) What is the core content of the work of special educators. 2) What is the role of a) inclusion and b) collaboration in their work?Method: The data for the study are current main laws and documents in both countries and curriculums of special educators in 5 universities in Finland and in 10 Universities in Sweden. A content analysis as well as critical discourse analysis are used with these documents and curriculums. Results: The results with regards to the curriculums will show the core areas in both countries as well as the differences in the content of studies. The legal documents will show the similarities and differences in regulations. In a previous study the core areas in curriculum for special education teachers students in Finland were reading, writing, mathematical and behavioral challenges (Hausstätter & Takala 2008). Sweden and special teachers and special pedagogs, Finland just special teachers. Sweden has education on more narrow areas, like mainly just on reading and writing challenges; in Finland special educators are general experts, studying more issues. Conclusions: The results are not ready yet, but we will be able to say about the differences and similarities as well as focus on the demands of inclusion in both countries after we have done the study.
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| 3. |
- Appel, Silke, et al.
(författare)
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Potential association of muscarinic receptor 3 gene variants with primary Sjogren's syndrome
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 70:7, s. 1327-1329
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary Sjögren's syndrome (pSS) is characterised by a chronic inflammation of exocrine glands. Salivary gland infiltrates, however, do not correlate well with disease symptoms, and a primary role for the salivary gland parenchyma in disease development has been suggested. Specifically, dysfunction of exocrine pathways involving the muscarinic receptor 3 (CHRM3) has been indicated. Objective: To investigate possible genetic divergence in the CHRM3 gene in patients with pSS. Methods: 530 patients with pSS and 532 controls from a combined Swedish and Norwegian cohort were genotyped for 84 single nucleotide polymorphisms (SNPs) distributed throughout CHRM3. Results: Genetic association was observed with five SNPs localised in intron 3 and 4 of CHRM3, the strongest being rs7548522 (minor allele frequency = 0.06, OR=1.93, 95% CI (1.24 to 3.01); p=0.0033). In addition, clinical parameters, including focus score, abnormal Schirmer's test and presence of autoantibodies, were associated with different SNPs in CHRM3. Conclusion: The study demonstrates a novel association of CHRM3 polymorphisms with pSS, suggesting a functional role for CHRM3 and the salivary gland parenchyma in the pathogenesis of pSS.
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| 4. |
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| 5. |
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| 6. |
- Berry, Joe Scott, et al.
(författare)
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Examining the biological pathways underlying clinical heterogeneity in Sjogren's syndrome : proteomic and network analysis
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:1, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Stratification approaches are vital to address clinical heterogeneity in Sjogren's syndrome (SS). We previously described that the Newcastle Sjogren's Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes.Method: We profiled serum proteins using O-link technology of 180 SS subjects. We used 5 O-link proteomics panels which included a total of 454 unique proteins. Network reconstruction was performed using the ARACNE algorithm, with differential expression estimates overlaid on these networks to reveal the key subnetworks of differential expression. Furthermore, data from a phase III trial of tocilizumab in SS were reanalysed by stratifying patients at baseline using NSST.Results: Our analysis highlights differential expression of chemokines, cytokines and the major autoantigen TRIM21 between the SS subtypes. Furthermore, we observe differential expression of several transcription factors associated with energy metabolism and redox balance namely APE1/Ref-1, FOXO1, TIGAR and BACH1. The differentially expressed proteins were inter-related in our network analysis, supporting the concept that distinct molecular networks underlie the clinical subtypes of SS. Stratification of patients at baseline using NSST revealed improvement of fatigue score only in the subtype expressing the highest levels of serum IL-6.Conclusions: Our data provide clues to the pathways contributing to the glandular and non-glandular manifestations of SS and to potential therapeutic targets for different SS subtypes. In addition, our analysis highlights the need for further exploration of altered metabolism and mitochondrial dysfunction in the context of SS subtypes.
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| 7. |
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| 8. |
- Björk, Albin, et al.
(författare)
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Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren's syndrome
- 2020
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Ingår i: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Standard assessment of interferon (IFN) system activity in systemic rheumatic diseases depends on the availability of RNA samples. In this study, we describe and evaluate alternative methods using plasma, serum and DNA samples, exemplified in the IFN-driven disease primary Sjogren's syndrome (pSS).Methods: Patients with pSS seropositive or negative for anti-SSA/SSB and controls were included. Protein-based IFN (pIFN) scores were calculated from levels of PD-1, CXCL9 and CXCL10. DNA methylation-based (DNAm) IFN scores were calculated from DNAm levels at RSAD2, IFIT1 and IFI44L. Scores were compared with mRNA-based IFN scores measured by quantitative PCR (qPCR), Nanostring or RNA sequencing (RNAseq).Results: mRNA-based IFN scores displayed strong correlations between B cells and monocytes (r=0.93 and 0.95, p<0.0001) and between qPCR and Nanostring measurements (r=0.92 and 0.92, p<0.0001). The pIFN score in plasma and serum was higher in patients compared with controls (p<0.0001) and correlated well with mRNA-based IFN scores (r=0.62-0.79, p<0.0001), as well as with each other (r=0.94, p<0.0001). Concordance of classification as 'high' or 'low' IFN signature between the pIFN score and mRNA-based IFN scores ranged from 79.5% to 88.6%, and the pIFN score was effective at classifying patients and controls (area under the curve, AUC=0.89-0.93, p<0.0001). The DNAm IFN score showed strong correlation to the RNAseq IFN score (r=0.84, p<0.0001) and performed well in classifying patients and controls (AUC=0.96, p<0.0001).Conclusions: We describe novel methods of assessing IFN system activity in plasma, serum or DNA samples, which may prove particularly valuable in studies where RNA samples are not available.
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| 9. |
- Bolstad, Anne Isine, et al.
(författare)
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Association between genetic variants in the tumour necrosis factor/lymphotoxin α/lymphotoxin β locus and primary Sjogren's syndrome in Scandinavian samples
- 2012
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 71:6, s. 981-988
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Lymphotoxin β (LTB) has been found to be upregulated in salivary glands of patients with primary Sjögren's syndrome (pSS). An animal model of pSS also showed ablation of the lymphoid organisation and a marked improvement in salivary gland function on blocking the LTB receptor pathway. This study aimed to investigate whether single-nucleotide polymorphisms (SNP) in the lymphotoxin α (LTA)/LTB/tumour necrosis factor (TNF) gene clusters are associated with pSS.METHODS:527 pSS patients and 532 controls participated in the study, all of Caucasian origin from Sweden and Norway. 14 SNP markers were genotyped and after quality control filtering, 12 SNP were analysed for their association with pSS using single marker and haplotype tests, and corrected by permutation testing.RESULTS:Nine markers showed significant association with pSS at the p=0.05 level. Markers rs1800629 and rs909253 showed the strongest genotype association (p=1.64E-11 and p=4.42E-08, respectively, after correcting for sex and country of origin). When the analysis was conditioned for the effect of rs1800629, only the association with rs909253 remained nominally significant (p=0.027). In haplotype analyses the strongest effect was observed for the haplotype rs909253G_rs1800629A (p=9.14E-17). The associations were mainly due to anti-Ro/SSA and anti-La/SSB antibody-positive pSS.CONCLUSIONS:A strong association was found between several SNP in the LTA/LTB/TNFα locus and pSS, some of which led to amino acid changes. These data suggest a role for this locus in the development of pSS. Further studies are needed to examine if the genetic effect described here is independent of the known genetic association between HLA and pSS.
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| 10. |
- Brauner, Susanna, et al.
(författare)
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H1N1 vaccination in Sjogren's syndrome triggers polyclonal B cell activation and promotes autoantibody production
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:10, s. 1755-1763
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesVaccination of patients with rheumatic disease has been reported to result in lower antibody titres than in healthy individuals. However, studies primarily include patients on immunosuppressive therapy. Here, we investigated the immune response of treatment-naive patients diagnosed with primary Sjogren's syndrome (pSS) to an H1N1 influenza vaccine.Methods Patients with Sjogren's syndrome without immunomodulatory treatment and age-matched and gender-matched healthy controls were immunised with an H1N1 influenza vaccine and monitored for serological and cellular immune responses. Clinical symptoms were monitored with a standardised form. IgG class switch and plasma cell differentiation were induced in vitro in purified naive B cells of untreated and hydroxychloroquine-treated patients and healthy controls. Gene expression was assessed by NanoString technology.ResultsSurprisingly, treatment-naive patients with Sjogren's syndrome developed higher H1N1 IgG titres of greater avidity than healthy controls on vaccination. Notably, off-target B cells were also triggered resulting in increased anti-EBV and autoantibody titres. Endosomal toll-like receptor activation of naive B cells in vitro revealed a greater propensity of patient-derived cells to differentiate into plasmablasts and higher production of class switched IgG. The amplified plasma cell differentiation and class switch could be induced in cells from healthy donors by preincubation with type 1 interferon, but was abolished in hydroxychloroquine-treated patients and after in vitro exposure of naive B cells to chloroquine.ConclusionsThis comprehensive analysis of the immune response in autoimmune patients to exogenous stimulation identifies a mechanistic basis for the B cell hyperactivity in Sjogren's syndrome, and suggests that caution is warranted when considering vaccination in non-treated autoimmune patients.
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