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Sökning: WFRF:(Miller FW) > (2020-2024)

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  • Zhou, D, et al. (författare)
  • Low copy numbers of complement C4 and C4A deficiency are risk factors for myositis, its subgroups and autoantibodies
  • 2023
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 82:2, s. 235-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complementC4in IIM pathology was unknown.MethodsWe elucidated the gene copy number (GCN) variations of totalC4,C4AandC4B, longandshort genesin 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion.ResultsThe large study populations helped establish the distribution patterns of variousC4GCN groups. Low GCNs ofC4T(C4T=2+3) andC4Adeficiency (C4A=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28–2.91), p=5.0×10−53forC4T, and 2.82 (2.48–3.21), p=7.0×10−57forC4Adeficiency. Contingency and regression analyses showed that among patients withC4Adeficiency, the presence ofHLA-DR3became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% hadHLA-DR3with an OR of 11.02 (1.44–84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies.ConclusionsC4Adeficiency is relevant in dermatomyositis,HLA-DRB1*03is important in IBM and bothC4Adeficiency andHLA-DRB1*03contribute interactively to risk of polymyositis.
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  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Lundberg, IE, et al. (författare)
  • Idiopathic inflammatory myopathies
  • 2021
  • Ingår i: Nature reviews. Disease primers. - : Springer Science and Business Media LLC. - 2056-676X. ; 7:1, s. 86-
  • Tidskriftsartikel (refereegranskat)
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