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

Objective: Guillain-Barre syndrome (GBS) is characterized by nerve infiltra tion of leukocytes and autoantibodies of the immunoglobulin GF (IgG) isotyp e directed against nerve constituents. Leukocyte receptors for IgG (Fc gamm a R) 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 Fc gamma R subclasses exhibit genetically determ ined biallelic functional polymorphisms (Fc gamma RIIa: R131 versus H131; F c gamma RIIIa: 158V versus 158F; Fc gamma RIIIb: NA1 versus NA2) that deter mine efficacy of the cellular immune response. To study the relevance of th ese polymorphisms for susceptibility and severity of GBS, we compared Fc ga mma R genotype distributions in GBS patients with those in controls. Method s: Genomic DNA was isolated from whole blood of 31 randomly selected patien ts with GBS and 187 healthy blood donors. Genotypes of the three polymorphi c Fc gamma R genes were determined by PCR. Results: Fc gamma RIIa-H131 homo zygosity was significantly increased in patients as compared with healthy c ontrols (OR 2.45; 95% CI 1.12 to 5.36; p = 0.037). Furthermore, Fc gamma RI Ia-H131 homozygous GBS patients had a higher risk for severe disease than d id patients with other genotypes (OR 18.57; 95% CI 1.95 to 176.49; p = 0.00 7). Conclusion: Fc gamma RIIa allotypes capable of initiating efficient cel lular effector functions are associated with increased risk for GBS and a m ore severe disease course. Fc gamma R alleles may constitute novel genetic risk markers for GBS.