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Limited effects of high-dose intravenous immunoglobulin (IVIg) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies
  1. Sevim Barbasso Helmers (sevim.barbasso{at}ki.se)
  1. Rheumatology Unit, Karolinska Institutet, Sweden
    1. Maryam Dastmalchi (maryam.dastmalchi{at}karolinska.se)
    1. Rheumatology Unit, Karolinska Institutet, Sweden
      1. Helene Alexanderson (helene.alexanderson{at}karolinska.se)
      1. Rheumatology Unit, Karolinska Institutet, Sweden
        1. Inger Nennesmo (inger.nennesmo{at}karolinska.se)
        1. Department of Pathology, Karolinska Institutet, Sweden
          1. Mona Esbjörnsson (mona.esbjornsson{at}ki.se)
          1. Division of Clinical Physiology, Karolinska Institutet, Sweden
            1. Björn Lindvall (bjorn.lindvall{at}orebroll.se)
            1. Muscular Centre, Örebro University Hospital, Sweden
              1. Ingrid E Lundberg (ingrid.lundberg{at}ki.se)
              1. Rheumatology Unit, Karolinska Institutet, Sweden

                Abstract

                Objectives: To achieve an improved understanding of the molecular mechanisms of high-dose intravenous immune globulin (IVIg) in inflammatory myopathies by investigating the effects on: muscle function and immunological molecules in skeletal muscle of polymyositis (PM)-, dermatomyositis (DM)- and inclusion body myositis (IBM) patients.

                Methods: Thirteen treatment resistant patients, 6 PM, 4 DM, 2 IBM, and 1 juvenile DM, were treated with 2g/kg of IVIg, 3 times with a monthly interval. Functional Index in Myositis, serum creatinine kinase (CK)-levels and muscle biopsies were performed before treatment and after the third IVIg infusion. Immunological molecules were also studied in biopsies taken 24-48hrs after first infusion.

                Results: Improved muscle function was observed in three patients (1PM, 1DM, 1IBM) and CK-levels decreased in five. T cells, macrophages, MHC class I antigen on muscle fibres, ICAM-1 and VCAM-1 expression and MAC- deposits on capillaries were present to an equal degree in biopsies before- and after IVIg treatment. No correlation between the clinical response and molecular changes was found.

                Conclusions: The clinical effects of high-dose IVIg on muscle function in patients with refractory inflammatory active myositis did not correspond with effects on any of the investigated molecules in our study. T cells, macrophages, phenotypical changes in muscle fibres and endothelial cell activation were still present after treatment. These observations question the role of IVIG as an immune modulating therapy in patients with inflammatory myopathies.

                • dermatomyositis (DM)
                • high-dose intravenous immuno globulin (IVIg)
                • inclusion body myositis (IBM)
                • muscle biopsy
                • polymyositis (PM)

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