Abstract
BackgroundIntravenous immunoglobulin (IVIg) is an effective treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, the optimal IVIg dose and regime is unknown. Polyvalent immunoglobulin (Ig) G form idiotypic/anti-idiotypic antibody pairs in serum and IVIg preparations. We determined IgG dimer levels before and after IVIg treatment in CIDP patients with the aim to explore their utility to serve as a surrogate marker for treatment response.MethodsIgG was purified from serum of five controls without treatment, as well as from serum of 16 CIDP patients, two patients with Miller Fisher syndrome (MFS), and one patient with myasthenia gravis before and after treatment with IVIg. IgG dimer levels were determined by size exclusion chromatography. IgG dimer formation was correlated with clinical response to IVIg treatment in CIDP. Re-monomerized IgG dimer fractions were analyzed for immunoreactivity against peripheral nerve tissue.ResultsIgG dimer levels were significantly higher in post- compared to pre-IVIg infusion samples. Low post-treatment IgG dimer levels in CIDP patients were associated with clinical worsening during IVIg treatment. Re-monomerized IgG dimer fractions from CIDP patients showed immunoreactivity against peripheral nerve tissue, whereas similarly treated samples from MFS patients showed immunoreactivity against GQ1b.ConclusionAssessment of IgG dimer levels could be a novel approach to monitor CIDP patients during IVIg treatment, but further studies in larger cohorts are warranted to explore their utility to serve as a potential therapeutic biomarker for IVIg treatment response in CIDP.
Highlights
Intravenous immunoglobulin (IVIg) is an effective treatment in chronic inflammatory demyelinating polyneuropathy (CIDP)
Patients were considered stable when Inflammatory Neuropathy Cause and Treatment (INCAT) score and Medical Research Council (MRC) sum score remained unchanged over 6 months of IVIg treatment, and worsening to IVIg treatment was defined as change of either INCAT or MRC sum score within 6 months
In CIDP patients, there was no association between IgG dimer levels pre- and post-IVIg treatment and age, body weight, or disease severity
Summary
Intravenous immunoglobulin (IVIg) is an effective treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). Intravenous immunoglobulin (IVIg) is considered the first-line treatment for CIDP, and several controlled studies demonstrated its short- and long-term efficacy [5,6,7]. The therapeutic effect of IVIg in CIDP is not fully understood, but it is believed that different modes of action are involved. These mechanisms include blockage or modulation of Fcγ-receptors, regulation of T cell and B cell activation, and alteration of inflammatory cytokines [8,9,10]. There is evidence from other autoimmune diseases that IVIg contains anti-idiotypic (anti-Id) antibodies that are able to neutralize pathological
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