Fc Receptor Polymorphisms, Disease Severity and Response to IVIG Treatment in Myasthenia Gravis (SC02.002)

Abstract

Objective: To study if one or more FcR polymorphisms are correlated with response to IVIG treatment in Myasthenia Gravis (MG). Background Intravenous immunoglobulin (IVIG) is an effective treatment of moderate to severe MG, but only about 60% of patients respond to treatment, and there are no clear predictors of response. Fc receptors play an important role in the mechanism of action of IVIG, so genetic variation of these might predict response to treatment. Design/Methods: 71 patients who participated in previous studies of IVIG efficacy, and new patients treated with IVIG for worsening MG were included. Patients were considered responders if the quantitative myasthenia gravis score (QMGS) improved by > 3.5 units 14 days after treatment. Polymorphisms within the FCγR2A, FCγR2B, FCγR3A and FCγR3B (NA1/NA2) genes were genotyped and the rates of treatment response were analyzed by each genotype. Results: The mean age was 56 years and 59% of patients were female. The mean QMGS at baseline was 13.4 ± 4.5. The FCγR2B-232I/I genotype was significantly more common in responders (94%) compared to non-responders (77%) (p=0.04). None of the other polymorphisms were associated with response. Patients with the FCγR2B 232I/I genotype had a higher QMGS at baseline (14 ± 5) compared to heterozygotes (10 ±2, p=0.025) and higher baseline QMGS was associated with response to treatment (responders: 15 ± 5; non-responders 12 ±4, p=0.01). Multivariate logistic regression analysis showed that only the baseline QMGS independently predicted response to IVIG (p=0.036). Conclusions: We found that the FCγR2B I/I genotype is associated with greater disease severity in MG and this, in turn, predicts a better response to IVIG. Although confirmation of this finding in larger population samples is required, the finding that the wild type inhibitory FcγR predisposes to more severe disease suggests that the FCγR2B does not act by directly inhibiting the pathogenic antibodies in MG. Supported by: An unrestricted educational grant from Talecris Biotherapeutics for clinician-initiated research. Disclosure: Dr. Barnett Tapia has nothing to disclose. Dr. Grinberg has nothing to disclose. Dr. Ghani has nothing to disclose. Dr. Rogaeva has nothing to disclose. Dr. St George-Hyslop has received personal compensation for activities with Finnegan LLC. Dr. Katzberg has received personal compensation for activities with Genzyme as a speaker and participant on an advisory board. Dr. Katzberg has received research support from Griffolds Biotherapeutics. Dr. Bril has received personal compensation for activities with Talecris Biotherapeutics as a consultant. Dr. Bril has received research support from Talecris Biotherapeutics.