Fcγ receptor IIIA genotype is associated with rituximab response in antimyelin-associated glycoprotein neuropathy

J Neurol Neurosurg Psychiatry. 2014 Aug;85(8):918-20. doi: 10.1136/jnnp-2013-306958. Epub 2014 Jan 31.

Abstract

Background: Treatment with anti-B cell antibody rituximab may ameliorate the disease course in a subgroup of patients with polyneuropathy associated with IgM monoclonal gammopathy. Polymorphisms of leukocyte IgG receptors (FcγR) that influence efficiency of antibody-dependent cell-mediated cytotoxicity determine rituximab efficacy in patients with lymphoma and autoimmune disease.

Objective: To investigate the association of FcγRIIA and FcγRIIIA polymorphisms with the response to rituximab treatment in a cohort of patients with polyneuropathy associated with IgM monoclonal gammopathy (PNP-IgM) with and without antimyelin-associated glycoprotein antibodies.

Methods: We determined FcγRIIA-R/H131 and FcγRIIIA-V/F158 genotypes in 27 patients with PNP-IgM using allele-specific PCR and Sanger sequencing.

Results: The FcγRIIIA-V/V158 genotype was associated with functional improvement (p=0.02) after 1 year.

Conclusions: FcγRIIIA polymorphisms are potential biomarkers for response to rituximab treatment in polyneuropathy associated with IgM monoclonal gammopathy.

Keywords: FC RECEPTOR; NEUROIMMUNOLOGY; NEUROPATHY; PARAPROTEINAEMIA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Cohort Studies
  • Demyelinating Diseases / drug therapy
  • Demyelinating Diseases / pathology
  • Female
  • Glycoproteins / physiology*
  • Humans
  • Male
  • Middle Aged
  • Myelin Sheath / immunology*
  • Myelin Sheath / pathology
  • Netherlands
  • Neural Conduction / physiology
  • Paraproteinemias / drug therapy
  • Paraproteinemias / genetics
  • Paraproteinemias / pathology
  • Polymorphism, Genetic
  • Polyneuropathies / drug therapy*
  • Polyneuropathies / genetics*
  • Polyneuropathies / pathology
  • Prospective Studies
  • Receptors, IgG / genetics*
  • Rituximab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • FCGR3A protein, human
  • Glycoproteins
  • Receptors, IgG
  • Rituximab