title: Intravenous immunoglobulin in patients with anti-GAD antibody-associated neurological diseases and patients with inflammatory myopathies: effects on clinicopathological features and immunoregulatory genes.
abstract: Controlled trials with intravenous immunoglobulin (IVIg) were conducted in patients with Stiff-Person Syndrome (SPS) and dermatomyositis (DM), two humorally mediated neurological disorders, and in inclusion body myositis (IBM), a T-cell-mediated inflammatory myopathy. The clinical efficacy was compared with alterations on tissue expression of complement, cytokines, chemokines, adhesion molecules, and immunoregulatory genes. The following patients were randomized in three separate trials to receive IVIg or placebo for 3 mo: (a) 16 patients with anti-GAD antibody-positive SPS; (b) 15 patients with DM resistant to therapies; and (c) 19 patients with IBM. After a washout, they crossed to the alternative therapy for another 3 mo. Efficacy was based on the difference in the respective disease scores from baseline to the second and third month of the infusions. In patients with SPS and DM, the scores changed positively and significantly from months 1 through 3, but returned to baseline when the patients crossed to placebo. In contrast, the scores in the placebo-randomized group remained constant or worsened from months 1 to 3, but improved significantly after crossing to IVIg. The muscle scores of patients with IBM did not significantly change between IVIg or placebo. In SPS, the anti-GAD65 antibody titers declined after IVIg but not after placebo. In DM, there was reduction of complement consumption, interception of membranolytic attack complex formation, downregulation of inflammation, fibrosis, cytokines, chemokines and adhesion molecules, and alterations in thousands of immunoregulatory genes. We conclude that IVIg is a safe and effective therapy for patients with SPS and DM unresponsive to other agents. In tissues, IVIg restores tissue cytoarchitecture by suppressing the inflammatory mediators at the protein, mRNA, and gene level.
authors.affiliation: Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. dalakasm@ninds.nih.gov
authors.forename: Marinos C
authors.initials: MC
authors.lastname: Dalakas
mesh_terms: D000328:Adult; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003165:Complement System Proteins / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D003882:Dermatomyositis / Q000188:drug therapy*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects; D018979:Myositis, Inclusion Body / Q000188:drug therapy*; D016750:Stiff-Person Syndrome / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007527:Isoenzymes; D003165:Complement System Proteins; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2