Fcgamma-receptor IIa polymorphism and the role of immunoadsorption in cardiac dysfunction in patients with dilated cardiomyopathy.
In patients with dilated cardiomyopathy (DCM), cardiac autoantibodies are able to bind with their Fab fragment to epitopes on cardiomyocytes, but thereafter they crosslink through their Fc fragment to cardiac Fc(gamma)-receptor IIa. Polymorphic variability of the Fc(gamma)-receptor IIa is associated with modified affinity of immunoglobin G (IgG) binding and may influence therapeutic effects. In this study, 103 consecutive DCM patients were treated with immunoadsorption (IA) therapy with subsequent IgG substitution (IA/IgG). Echocardiography was performed at baseline and again at 3 and 6 months after IA/IgG. Fc(gamma)-receptor IIa polymorphism R/H131 was genotyped using a nested sequence-specific primer polymerase chain reaction (PCR). Patients with the Fc(gamma)-receptor IIa genotype R/R131 showed significantly greater improvement in left ventricular (LV) function than patients with the R/H131 or H/H131 genotypes did. Irrespective of the Fc(gamma)-receptor polymorphism, patients with shorter disease duration and a more impaired LV function responded with a greater increase in LV ejection fraction (LVEF). Therefore, the Fc(gamma)-receptor polymorphism influences the efficacy of immunomodulatory therapy involving IA/IgG.
Staudt
A
A
Department of Internal Medicine B, Ernst-Moritz-Arndt-University, Greifswald, Germany. staudt@uni-greifswald.de
Herda
L R
LR
Trimpert
C
C
Lubenow
L
L
Landsberger
M
M
Dörr
M
M
Hummel
A
A
Eckerle
L G
LG
Beug
D
D
Müller
C
C
Hoffmann
W
W
Weitmann
K
K
Klingel
K
K
Kandolf
R
R
Kroemer
H K
HK
Greinacher
A
A
Felix
S B
SB
D001323:Autoantibodies / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000503:physiopathology*; D004452:Echocardiography; D000939:Epitopes; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007163:Immunosorbent Techniques; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000503:physiopathology
D001323:Autoantibodies; D000939:Epitopes; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D017452:Receptors, IgG