title: Pharmacokinetics of intravenous immunoglobulin in multifocal motor neuropathy.
abstract: BACKGROUND
  Multifocal motor neuropathy (MMN) is often responsive to treatment with intravenous immunoglobulin (IVIg), but the optimal dose and intervals of IVIg maintenance treatment have not been established. Increase in IgG concentration (ΔIgG) after IVIg infusion has recently been identified as determinant of outcome in Guillain-Barré syndrome. ΔIgG may therefore represent a potentially useful biomarker to optimise IVIg dosing in patients with MMN.
  
  
  OBJECTIVE
  The aims of this study were to determine variability of IVIg pharmacokinetics in patients with MMN in relation to treatment response, and to establish whether interindividual differences in IVIg pharmacokinetics were associated with genetic polymorphisms of the endothelial IgG receptor (FcRn) which determines IgG half-life.
  
  
  METHODS
  Twenty-three patients with MMN receiving their first IVIg treatment at a cumulative dose of 2.0 g/kg in 5 days were included. A good treatment response was defined as an increase in muscle strength of at least one Medical Research Council point in minimally two muscle groups. IgG concentrations in serum were determined at baseline, at day 1 and day 5 of the IVIg course, and 3 weeks after treatment. FcRn copy number variation and differences in repeat length of the variable number of tandem repeats in the FcRn gene were determined by quantitative PCR and Sanger sequencing.
  
  
  RESULTS
  Seventeen patients (74%) had a good response to treatment. Total IgG and ΔIgG levels showed large variation between patients. Mean ΔIgG was higher in IVIg responders than in non-responders, with the largest difference on day 1 (11.1 g/L vs 4.5 g/L, p=0.06), but our study lacked power to show statistically significant differences. Genetic variation in the FcRn gene was not associated with ΔIgG levels or response to treatment.
  
  
  CONCLUSIONS
  IVIg pharmacokinetics varies in patients with MMN and may be associated with clinical response.
authors: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Lotte
authors: L
authors: Vlam
authors: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Elisabeth A
authors: EA
authors: Cats
authors: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Eline
authors: E
authors: Willemse
authors: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Hessel
authors: H
authors: Franssen
authors: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Jelena
authors: J
authors: Medic
authors: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Sanne
authors: S
authors: Piepers
authors: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Jan H
authors: JH
authors: Veldink
authors: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Leonard H
authors: LH
authors: van den Berg
authors: Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: W-Ludo
authors: WL
authors: van der Pol
mesh_terms: D000328:Adult; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D016472:Motor Neuron Disease / Q000188:drug therapy*; D053580:Muscle Strength / Q000187:drug effects; D011115:Polyneuropathies / Q000188:drug therapy*; D011961:Receptors, Fc / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D011961:Receptors, Fc; C100688:Fc receptor, neonatal
keywords: Neuroimmunology; Neuropathy