Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies.

Abstract

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.

• Authors: Sevim Barbasso Helmers, Maryam Dastmalchi, Helene Alexanderson, Inger Nennesmo, Mona Esbjörnsson, Björn Lindvall, Ingrid E Lundberg
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 66 Issue 10 Pg. 1276-83 (Oct 2007) ISSN: 0003-4967 [Print] England
• PMID: 17277004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Complement Membrane Attack Complex
• Histocompatibility Antigens Class I
• Histocompatibility Antigens Class II
• Immunoglobulins, Intravenous
• Interleukin-1alpha
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Creatine Kinase

Topics

• Adolescent
• Aged
• Antigens, CD (immunology)
• Complement Membrane Attack Complex (immunology)
• Creatine Kinase (blood)
• Dermatomyositis (drug therapy, immunology)
• Drug Administration Schedule
• Female
• Histocompatibility Antigens Class I (immunology)
• Histocompatibility Antigens Class II (immunology)
• Humans
• Immunoglobulins, Intravenous (administration & dosage)
• Immunohistochemistry (methods)
• Intercellular Adhesion Molecule-1 (immunology)
• Interleukin-1alpha (immunology)
• Male
• Middle Aged
• Muscle, Skeletal (immunology)
• Myositis (drug therapy, immunology)
• Myositis, Inclusion Body (drug therapy, immunology)
• Polymyositis (drug therapy, immunology)
• Vascular Cell Adhesion Molecule-1 (immunology)