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Sökning: WFRF:(Klareskog Lars) > Örebro universitet

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1.
  • Franks, P. W., et al. (författare)
  • Technological readiness and implementation of genomic-driven precision medicine for complex diseases
  • 2021
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:3, s. 602-620
  • Forskningsöversikt (refereegranskat)abstract
    • The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.
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2.
  • Jónsdóttir, Thorunn, et al. (författare)
  • Treatment of refractory SLE with rituximab plus cyclophosphamide : clinical effects, serological changes, and predictors of response
  • 2008
  • Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 67:3, s. 330-334
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate efficacy, serological responses, and predictors of response in patients with severe and refractory systemic lupus erythematosus (SLE) treated with rituximab plus cyclophosphamide.METHODS: 16 patients entered a treatment protocol using rituximab plus cyclophosphamide. Disease activity was assessed by the SLE disease activity index (SLEDAI) and by the British Isles Lupus Assessment Group (BILAG) index.RESULTS: At six months follow up, mean SLEDAI values decreased significantly from (mean (SD)) 12.1 (2.2) to 4.7 (1.1). Clinical improvement (50% reduction in SLEDAI) occurred in all but three patients. All but one patient responded according to BILAG. Remission defined as SLEDAI <3 was achieved in nine of 16 patients. Isotype analysis of anti-dsDNA antibodies revealed preferential decreases of IgG and IgA, but not IgM. Higher absolute numbers of CD19+ cells at baseline were correlated with shorter depletion time (r = -0.6).CONCLUSIONS: The majority of patients improved following rituximab plus cyclophosphamide. The differential downregulation of anti-DNA of the IgG and IgA but not the IgM isotypes supports the hypothesis that cells producing pathogenic autoantibodies are preferentially targeted by the treatment. The fact that greater absolute numbers of CD19+ cells at baseline predict a less impressive clinical and serological response suggests that more flexible dosing could be advantageous.
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3.
  • Magnusson, Patrik K. E., et al. (författare)
  • The Swedish Twin Registry : establishment of a biobank and other recent developments
  • 2013
  • Ingår i: Twin Research and Human Genetics. - Cambridge, United Kingdom : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 16:1, s. 317-329
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.
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4.
  • van Vollenhoven, Ronald F., et al. (författare)
  • Biopsy-verified response of severe lupus nephritis to treatment with rituximab (anti-CD20 monoclonal antibody) plus cyclophosphamide after biopsy-documented failure to respond to cyclophosphamide alone
  • 2004
  • Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 33:6, s. 423-427
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The monoclonal anti-B cell antibody rituximab (Rituxin, Mabthera) may be of benefit in antibody-driven diseases, including systemic lupus erythematosus (SLE) nephritis.PATIENTS AND TREATMENT: Two female patients with biopsy-confirmed severe and active SLE nephritis despite treatment with cyclophosphamide (CyX) were given four rituximab infusions plus two additional CyX infusions.RESULTS: Both patients tolerated the treatment well and SLE activity improved. On repeat kidney biopsy after the combined treatment, Patient 1 showed a profound reduction of nephritis activity, and she was maintained on low-dose prednisolone only. A repeat biopsy after 1 year confirmed the sustained reduction of lupus nephritis activity. In Patient 2, rebiopsy after combined treatment also showed a significant reduction in disease activity.CONCLUSION: These cases provide histopathological documentation of a significant treatment benefit from rituximab plus CyX in two patients refractory to CyX alone. This combination is being explored further as salvage therapy for such CyX-resistant patients.
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