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- Khatri, B., et al.
(författare)
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Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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| 5. |
- Amkreutz, J. A. M. P., et al.
(författare)
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Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis
- 2021
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Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 73:6, s. 921-930
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Autoantibodies, such as anti–citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts. Methods: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations. Results: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm2 (95% confidence interval [95% CI] 0.91–0.93) versus 0.95 g/cm2 (95% CI 0.93–0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08–0.29] versus 0.48 [95% CI 0.33–0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti–carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time. Conclusion: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed. © 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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- Dominique, Matilda, et al.
(författare)
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Strukturbiblioteket
- 2020
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- "Projektet Strukturbiblioteket påbörjades under 2016, och presenterades i en utställning på Konsthantverkarnas galleri vid Slussen i Stockholm i september 2017. Sedan dess har jag fortsatt att arbeta utifrån idéer, prover, former och material som kommer ur projektet. I denna publikation, som består av fyra delar, har jag samlat lite av det material som producerats under projektet: texter, fotografier, anteckningar och skisser. Den textila strukturens bärighet är ett ämne som jag ofta återkommer till i mitt arbete. På detaljnivå handlar det om att varje tråds närvaro blir lika viktig som den nästa, och i ett större perspektiv där det textila materialet sätts i relation till samtid och historia. Genom vävningen vill jag ställa frågor om idéer kring vad textil är och anses vara, om textil närvaro i olika rum, om vävning som ingenjörskonst och om hur minnen kan vara inbyggda i en idé om ett material. I vävstolen handlar arbetet om hur väven påverkas av material, garnkvalitet, teknik och hur garnet färgas in. Genom att arbeta med samma teknik under en längre tid och låta den prövas med olika typer av trådar och i olika skalor skapar jag mig inte bara en förståelse för dess uppbyggnad, utan försöker också komma närmare olika berättelser som formar en specifik vävtekniks historia. Strukturbiblioteket är en studie av tekniken våffelväv där jag har byggt upp en liten samling skulpturala textilier som alla är vävda på samma sätt. Med olika typer av ullgarn har jag velat formulera mig kring vad våffelvävens struktur är kapabel till och hur idéer om denna typ av väv kan utmanas. Under arbetet i vävstolen har jag undersökt hur garnets grovlek, uppbyggnad och textur påverkar skalan och den vävda formen. I olika utställningsrum har jag senare prövat hur väven kan upplevas som tredimensionellt objekt. Resultatet är 30 st vävprover och en serie större, rumsliga verk." Text: Marcia Harvey Isaksson, Johanna Theander, Linda Wiktorén, Matilda Dominique Foto: Elin Sylwan, Matilda Dominique Formgivning: Emilie Mottet
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| 7. |
- Geale, Kirk, et al.
(författare)
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Persistence of biologic treatments in psoriatic arthritis : a population-based study in Sweden
- 2020
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Ingår i: Rheumatology. - : Oxford University Press. - 2514-1775. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: TNF inhibitors (TNFis) and IL inhibitors are effective treatments for PsA. Treatment non-persistence (drug survival, discontinuation) is a measure of effectiveness, tolerability and patient satisfaction or preferences in real-world clinical practice. Persistence on these treatments is not well understood in European PsA populations. The aim of this study was to compare time to non-persistence for either ustekinumab (IL-12/23 inhibitor) or secukinumab (IL-17 inhibitor) to a reference group of adalimumab (TNFi) treatment exposures in PsA patients and identify risk factors for non-persistence.Methods: A total of 4649 exposures of adalimumab, ustekinumab, and secukinumab in 3918 PsA patients were identified in Swedish longitudinal population-based registry data. Kaplan-Meier curves were constructed to measure treatment-specific real-world risk of non-persistence and adjusted Cox proportional hazards models were estimated to identify risk factors associated with non-persistence.Results: Ustekinumab was associated with a lower risk of non-persistence relative to adalimumab in biologic-naive [hazard ratio (HR) 0.48 (95% CI 0.33, 0.69)] and biologic-experienced patients [HR 0.65 (95% CI 0.56, 0.76)], while secukinumab was associated with a lower risk in biologic-naive patients [HR 0.65 (95% CI 0.49, 0.86)] but a higher risk of non-persistence in biologic-experienced patients [HR 1.20 (95% CI 1.03, 1.40)]. Biologic non-persistence was also associated with female sex, axial involvement, recent disease onset, biologic treatment experience and no psoriasis.Conclusion: Ustekinumab exhibits a favourable treatment persistency profile relative to adalimumab overall and across lines of treatment. The performance of secukinumab is dependent on biologic experience. Persistence and risk factors for non-persistence should be accounted for when determining an optimal treatment plan for patients.
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| 8. |
- Sena, AG, et al.
(författare)
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FIRST LINE TREATMENT WITH CONVENTIONAL SYNTHETIC DISEASE MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATOID ARTHRITIS: A MULTINATIONAL POPULATION-BASED COHORT FROM 14 REAL WORLD HEALTHCARE DATABASES AND 9 COUNTRIES - REALITY VERSUS GUIDELINES
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 327-327
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Treatment guidelines recommend early initiation of csDMARDs following diagnosis of rheumatoid arthritis (RA), with methotrexate (MTX) as first-line therapy. Scarce evidence exists on adherence to this guidanceObjectives:To characterize first-line csDMARD treatment during the first year following an RA diagnosis.Methods:14 real world databases (3 Primary care, 6 primary/secondary care records, 5 claims) from 9 countries were included, all mapped to the OMOP common data model.Patients were included on the earliest event of: 1st diagnosis of RA or 1st DMARD prescription with an RA diagnosis within 30 days. Patients were >18 years-old, required 1+ year pre-index data, and at least 1-year follow-up. Study period covered 2000-2018. Previous users of DMARDs or non-RA inflammatory arthritis history were excluded. Only MTX, Hydroxychloroquine (HCQ), Sulfasalazine (SSZ) and Leflunomide (LEF) were available in all databases.Results:We identified 323,547 eligible participants. Large variation was observed internationally (Figure 1). MTX as first-line monotherapy ranged from 33.3% to 74.5%, and in combination with HCQ from 2.1% to 6.7%. Three additional csDMARDs were used as first-line: HCQ in 10.1% to 30.2%, SSZ in 0.9% to 28.7%, and LEF in 1.8% to 15.2%.Figure 1.First line csDMARD treatment during 1yr from first observed RA diagnosisConclusion:We report wide heterogeneity of first-line csDMARDs regimens internationally. Despite recommendations for MTX to be first line therapy, data suggest that a large proportion of patients receive alternative csDMARD.Disclosure of Interests: :Anthony G Sena Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Full-time employment salary from Janssen, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, Denis Granados: None declared, Nigel Hughes Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, WALID FAKHOURI Shareholder of: E Lilly Shares, Employee of: Eli Lilly and Company, Antje Hottgenroth Shareholder of: Eli Lilly shares, Employee of: Lilly Deutschland GmbH, Raivo Kolde: None declared, Sulev Reisberg: None declared, Carmen Olga Torre: None declared, Talita Duarte-Salles: None declared, Yesika Díaz: None declared, Jose Felipe Golib-Dzib Grant/research support from: Full-time employment salary from Janssen, Employee of: Yes, Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Emily S. Brouwer Shareholder of: J&J shares, Takeda shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Edward Burn: None declared, Jennifer Lane: None declared, David Vizcaya Employee of: Bayer, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB, Marcel de Wilde: None declared, Katia Verhamme: None declared, Peter Rijnbeek: None declared, Elke Theander Employee of: Janssen-Cilag Sweden AB, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Patrick Ryan: None declared
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