Fcγ receptor IIIA genotype is associated with rituximab response in antimyelin-associated glycoprotein neuropathy.
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.
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
Abraham C J
AC
Stork
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
Nicolette C
NC
Notermans
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
Leonard H
LH
van den Berg
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
Raymond D
RD
Schellevis
Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands.
Jikke-Mien F
JM
Niermeijer
Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Maaike
M
Nederend
Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Jeanette H W
JH
Leusen
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
W-Ludo
WL
van der Pol
D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D015331:Cohort Studies; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009186:Myelin Sheath / Q000276:immunology* / Q000473:pathology; D009426:Netherlands; D009431:Neural Conduction / Q000502:physiology; D010265:Paraproteinemias / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D011110:Polymorphism, Genetic; D011115:Polyneuropathies / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics*; D000069283:Rituximab; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; C496124:FCGR3A protein, human; D006023:Glycoproteins; D017452:Receptors, IgG; D000069283:Rituximab
FC RECEPTOR; NEUROIMMUNOLOGY; NEUROPATHY; PARAPROTEINAEMIA