IgG receptor IIa alleles determine susceptibility and severity of Guillain-Barré syndrome.

Abstract:

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). CONCLUSION: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.

journal_name

Neurology

journal_title

Neurology

authors

van der Pol WL,van den Berg LH,Scheepers RH,van der Bom JG,van Doorn PA,van Koningsveld R,van den Broek MC,Wokke JH,van de Winkel JG

doi

10.1212/wnl.54.8.1661

subject

Has Abstract

pub_date

2000-04-25 00:00:00

pages

1661-5

issue

8

eissn

0028-3878

issn

1526-632X

journal_volume

54

pub_type

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