Immunoglobulin G Fc-receptor (FcgammaR) IIA and IIIB polymorphisms related to disability in MS.
OBJECTIVE
MS is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of immunoglobulin G (IgG) (FcgammaR) link the humoral and cellular immune responses by targeting immune complexes to effector cells. Different FcgammaR show variability in their distribution, strength, and capacity of binding different IgG subclasses.


METHODS
To investigate the role of FcgammaR in MS, 136 MS patients and 96 matched controls were genotyped for FcgammaRIIA and FcgammaRIIIB gene polymorphisms; the results were correlated to disease susceptibility and severity measured by the Expanded Disability Status Scale (EDSS).


RESULTS
The allele frequencies of the FcgammaRIIA and FcgammaRIIIB did not differ significantly between the MS patients and the controls. Patients homozygous for the FcgammaRIIIB neutrophil antigen (NA) 1 allele had a significantly more benign course of MS than patients heterozygous or homozygous for the FcgammaRIIIB NA2 allele. Patients homozygous for the FcgammaRIIA histidine (H) allele also had a more benign course of MS than patients heterozygous or homozygous for the FcgammaRIIA arginine (R) allele.


CONCLUSIONS
The results implicate FcgammaRIIIB and to a lesser extent FcgammaRIIA as disease-modifying genes in MS. FcgammaRIIIB NA1/NA1 and FcgammaRIIA H/H bind more efficient IgG1/IgG3 and IgG2 subclasses, respectively, than FcgammaRIIIB NA2/NA2 and FcgammaRIIA R/R. A more effective processing of circulating immune complexes may be one mechanism for better clinical outcome in MS.
Myhr
K M
KM
Department of Neurology, Haukeland Hospital, University of Bergen, Norway. Kjell.M.Myhr@nevro.haukeland.no
Raknes
G
G
Nyland
H
H
Vedeler
C
C
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D004185:Disability Evaluation; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011961:Receptors, Fc / Q000235:genetics*
D007074:Immunoglobulin G; D011961:Receptors, Fc