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- Espinosa Ortega, Hector Fabricio
(författare)
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Studies on autoantibodies and inflammatory markers in patients with idiopathic inflammatory myopathies
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic Inflammatory myopathies (IIM), commonly known as myositis, are chronic autoimmune diseases characterized by low muscle strength and low muscle endurance as main features. However, a high number of patients may develop extra muscular manifestations such as interstitial lung disease, skin rash or arthritis. There are known genetic and environmental risk factors for developing these conditions, but the cause is not fully understood. To date, it is considered that myositis is driven by an autoimmune component. In this sense, the production of autoantibodies is characteristic in most patients and each of these autoantibodies is strongly linked to specific clinical manifestations. However, the implications of positive autoantibodies as prognostics tools beyond the association with clinical features has not been fully studied. Moreover, different methods have been used to detect these autoantibodies and new methods, usually employed in the daily clinical setting, require validation. In addition to the autoantibodies, the role of inflammatory markers as predictors of subjective health perception has been overlooked in patients with myositis. The aim of this thesis was to validate an autoantibody assay commonly used in the clinic, a line blot assay, as well as to explore the usefulness of autoantibodies as predictors of response to treatment and organ damage, and to investigate the association of inflammatory markers with patient reported outcomes. A validation of a line bot test was conducted using an immunoprecipitation-based algorithm as comparator in a cohort of well-characterized patients with myositis. The prevalence of relevant clinical associations with both assays was compared between patients. A moderate agreement between the assays was found, and the clinical features of patients with detected autoantibodies by the line blot assay were consistent with known clinical phenotypes (Paper I). By using a longitudinal Swedish electronic database (SweMyoNet), dermatomyositis specific autoantibodies (DMSA) were found as predictors for moderate level of response to treatment; initial doses of glucocorticoids and shorter time lag from first symptoms to diagnosis were also predictors of response to treatment (Paper II). In a longitudinal study, based on a large international electronic database (MyoNet), patients with anti-PM/Scl autoantibodies accumulated damage more pronounced than seronegative patients, and patients with DMSA accumulated less pronounced damage than seronegative patients. Furthermore, a strong correlation between severity of muscle damage and functional disability was found, especially in patients with immune-mediated necrotizing myopathies (Paper III). By analyzing data from MyoNet, we found a longitudinal correlation between Patient Global Assessment (PatGA) and inflammatory markers, namely C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (Paper IV). Altogether, the findings of this thesis indicate that the line blot assay is useful to detect the most frequent autoantibodies in patients with a known myositis diagnosis. The results of this thesis also suggest that autoantibodies are useful as predictors of response to treatment and of organ damage, and that inflammatory markers are associated with subjective health perception status measured by the Patient Global Assessment scale in patients with myositis.
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- Lodin, Karin, et al.
(författare)
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Patient global assessment and inflammatory markers in patients with idiopathic inflammatory myopathies : A longitudinal study
- 2024
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Ingår i: Seminars in Arthritis & Rheumatism. - : Elsevier. - 0049-0172 .- 1532-866X. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- AimTo explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM).MethodsPGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models. Mediation analysis was used to test if the association between PGA and inflammatory markers during the first year of observation could be explained by measures of disease activity and function.ResultsPGA improved, and inflammatory markers decreased during the first year of observation. In the mixed models, high levels of inflammatory markers were associated with worse PGA in both men and women across time points during five years of observation. In men, but not in women, the association between elevated ESR, CRP and poorer PGA was explained by measures of function and disease activity. With a few exceptions, the association between improved PGA and reduced inflammatory markers was partially mediated by improvements in all measures of function and disease activity.ConclusionIncreased levels of systemic inflammation are associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health in patients with IIM. Furthermore, the results demonstrate the importance of incorporating PGA as an outcome measure in clinical practice and clinical trials.
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