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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 Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
² Rheumatology Unit, Department of Medicine, Department of Physical Therapy, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
³ Department of Pathology, Karolinska University Hospital, Huddinge, Karolinska Institutet, Stockholm, Sweden
⁴ Division of Clinical Physiology, Department of Medical Laboratory Medicine, Karolinska University Hospital, Huddinge, Karolinska Institutet, Stockholm, Sweden
⁵ Neuromuscular Unit, Division of Neurology, Department of Clinical Neurosciences and Locomotion, University Hospital, Linköping; Muscular Centre, Department of Neurology, University Hospital, Örebro, Sweden

Correspondence to:
Sevim Barbasso Helmers, Karolinska University Hospital, Rheumatology Unit, CMM L8:04, SE-171 76 Stockholm, Sweden; Sevim.Barbasso{at}ki.se

Objectives: The study was conducted with the aim of achieving an improved understanding of the molecular mechanisms of high-dose intravenous immunoglobulin (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 2 g/kg of IVIG, three times at monthly intervals. Functional Index in Myositis and serum creatinine kinase (CK) levels were determined, and muscle biopsies were performed before treatment and after the third IVIG infusion. Immunological molecules were also studied in biopsies taken 24–48 h after the first infusion.

Results: Improved muscle function was observed in three patients (1 PM, 1 DM and 1 IBM) and CK levels decreased in five. T cells, macrophages, major histocompatibility complex (MHC) class I antigen on muscle fibres, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and membranolytic attack complex (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 to 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 a role for IVIG as an immune-modulating therapy in patients with inflammatory myopathies.

Abbreviations: CD, cluster of differentiation; CK, creatinine kinase; DM, dermatomyositis; FI, Functional Index in Myositis; IBM, inclusion body myositis; ICAM intercellular adhesion molecule, ; IL, interleukin; IVIG, intravenous immunoglobulin; MAC, membranolytic attack complex; MHC, major histocompatibility complex; PBMC, peripheral blood mononuclear cell; PM, polymyositis; VCAM, vascular cell adhesion molecule