IgG receptor IIa alleles determine susceptibility and severity of Guillain-Barré syndrome.
OBJECTIVE
Guillain-Barré syndrome (GBS) is characterized by nerve infiltration of leukocytes and autoantibodies of the immunoglobulin G (IgG) isotype directed against nerve constituents. Leukocyte receptors for IgG (FcgammaR) constitute an important link between the humoral and cellular parts of the immune system and confer potent cellular effector functions to myelin-directed antibodies. Three FcgammaR subclasses exhibit genetically determined biallelic functional polymorphisms (FcgammaRIIa: R131 versus H131; FcgammaRIIIa: 158V versus 158F; FcgammaRIIIb: NA1 versus NA2) that determine efficacy of the cellular immune response. To study the relevance of these polymorphisms for susceptibility and severity of GBS, we compared FcgammaR genotype distributions in GBS patients with those in controls.


METHODS
Genomic DNA was isolated from whole blood of 31 randomly selected patients with GBS and 187 healthy blood donors. Genotypes of the three polymorphic FcgammaR genes were determined by PCR.


RESULTS
FcgammaRIIa-H131 homozygosity was significantly increased in patients as compared with healthy controls (OR 2.45; 95% CI 1.12 to 5.36; p = 0.037). Furthermore, FcgammaRIIa-H131 homozygous GBS patients had a higher risk for severe disease than did patients with other genotypes (OR 18.57; 95% CI 1.95 to 176.49; p = 0.007).


CONCLUSIONS
FcgammaRIIa allotypes capable of initiating efficient cellular effector functions are associated with increased risk for GBS and a more severe disease course. FcgammaR alleles may constitute novel genetic risk markers for GBS.
van der Pol
W L
WL
Departments of Immunology, University Hospital Utrecht, Utrecht, The Netherlands.
van den Berg
L H
LH
Scheepers
R H
RH
van der Bom
J G
JG
van Doorn
P A
PA
van Koningsveld
R
R
van den Broek
M C
MC
Wokke
J H
JH
van de Winkel
J G
JG
D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000235:genetics* / Q000276:immunology; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009844:Oligosaccharides / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics*; D018570:Risk Assessment; D012720:Severity of Illness Index
D015703:Antigens, CD; D001323:Autoantibodies; D015415:Biomarkers; C080568:Fc gamma receptor IIA; D009844:Oligosaccharides; D017452:Receptors, IgG; C037563:G(M1)-oligosaccharide