Km. Myhr et al., Immunoglobulin G Fc-receptor (Fc gamma R) IIA and IIIB polymorphisms related to disability in MS, NEUROLOGY, 52(9), 1999, pp. 1771-1776
Objective: MS is immunologically mediated in genetically susceptible indivi
duals. Receptors for the Fc fragment of immunoglobulin G (IgG) (Fc gamma R)
link the humoral and cellular immune responses by targeting immune complex
es to effector cells. Different Fc gamma R show variability in their distri
bution, strength, and capacity of binding different IgG subclasses. Methods
: To investigate the role of Fc gamma R in MS, 136 MS patients and 96 match
ed controls were genotyped for Fc gamma RIIA and Fc gamma RIIIB gene polymo
rphisms; the results were correlated to disease susceptibility and severity
measured by the Expanded Disability Status Scale (EDSS). Results: The alle
le frequencies of the Fc gamma RIIA and Fc gamma RIIIB did not differ signi
ficantly between the MS patients and the controls. Patients homozygous for
the Fc gamma RIIIB neutrophil antigen (NA) I allele had a significantly mor
e benign course of MS than patients heterozygous or homozygous for the Fc g
amma RIIIB NA2 allele. Patients homozygous for the Fc gamma RIIA histidine
(H) allele also had a more benign course of MS than patients heterozygous o
r homozygous for the Fc gamma RIIA arginine (R) allele. Conclusion: The res
ults implicate Fc gamma RIIIB and to a lesser extent Fc gamma RIIA as disea
se-modifying genes in MS. Fc gamma RIIIB NA1/NA1 and Fc gamma RIIA H/H bind
more efficient IgG1/IgG3 and IgG2 subclasses, respectively, than Fc gamma
RIIIB NA2/NA2 and Fc gamma RIIA R/R. A more effective processing of circula
ting immune complexes may be one mechanism for better clinical outcome in M
S.