title: Fcgamma-receptor IIa polymorphism and the role of immunoadsorption in cardiac dysfunction in patients with dilated cardiomyopathy.
abstract: 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.
authors.affiliation: Department of Internal Medicine B, Ernst-Moritz-Arndt-University, Greifswald, Germany. staudt@uni-greifswald.de
authors.forename: A
authors.initials: A
authors.lastname: Staudt
authors.forename: L R
authors.initials: LR
authors.lastname: Herda
authors.forename: C
authors.initials: C
authors.lastname: Trimpert
authors.forename: L
authors.initials: L
authors.lastname: Lubenow
authors.forename: M
authors.initials: M
authors.lastname: Landsberger
authors.forename: M
authors.initials: M
authors.lastname: Dörr
authors.forename: A
authors.initials: A
authors.lastname: Hummel
authors.forename: L G
authors.initials: LG
authors.lastname: Eckerle
authors.forename: D
authors.initials: D
authors.lastname: Beug
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: W
authors.initials: W
authors.lastname: Hoffmann
authors.forename: K
authors.initials: K
authors.lastname: Weitmann
authors.forename: K
authors.initials: K
authors.lastname: Klingel
authors.forename: R
authors.initials: R
authors.lastname: Kandolf
authors.forename: H K
authors.initials: HK
authors.lastname: Kroemer
authors.forename: A
authors.initials: A
authors.lastname: Greinacher
authors.forename: S B
authors.initials: SB
authors.lastname: Felix
mesh_terms: 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
chemical_list: D001323:Autoantibodies; D000939:Epitopes; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D017452:Receptors, IgG