title: The Fc gammaRIIa polymorphism R/H131, autoantibodies against the platelet receptors GPIb alpha and Fc gammaRIIa and a risk for thromboembolism in lupus anticoagulant patients.
abstract: There is a clear propensity of individuals with lupus anticoagulant (LA) for thromboembolic disease (TE). Yet, it is not clear how individuals at risk for TE can be differentiated from those who are not. The Fc gammaRIIa receptor is the only Fc receptor expressed by platelets. As platelets can be activated via this receptor, we have compared gene frequencies of the Fc gammaRIIa polymorphism R/H131 in 46 and 27 patients with (LA/TE+) and without TE (LA/TE-), respectively, in an exploratory study. Furthermore, we investigated the presence of autoantibodies against Fc gammaRIIa and/or GPIb alpha, which is in close proximity to the Fc gammaRIIa and interacts with it functionally, and a possible linkage of antibody formation to HLA class II alleles. The Fc gammaRIIa-R/R131 genotype was significantly less frequent in patients with LA compared to controls (p<0.025). These findings were due to an increased frequency of heterozygous patients in the LA/TE+ cohort (odds ratio 6.76, 95% confidence interval 1.55-62.03, p<0.008). For the first time, heterozygosity, rather than homozygosity, can be linked to disease, which may be explained by the dual function of the Fc gammaRIIa, namely binding of antibodies to platelets and thereby their activation, and, on the other hand, clearance of antibody coated platelets by the phagocyte system. There was no correlation between the presence of anti-Fc gammaRIIa or anti-GPIb alpha autoantibodies and the Fc gammaRIIa-R/H131 polymorphism, nor the incidence of TE, nor HLA class II alleles.
authors.affiliation: Clinic for Blood Group Serology, Medical University Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schallmoser
authors.forename: Christiane
authors.initials: C
authors.lastname: Rosin
authors.forename: Regina
authors.initials: R
authors.lastname: Knittelfelder
authors.forename: Thomas
authors.initials: T
authors.lastname: Sailer
authors.forename: Silvia
authors.initials: S
authors.lastname: Ulrich
authors.forename: Claudia
authors.initials: C
authors.lastname: Zoghlami
authors.forename: Stephan
authors.initials: S
authors.lastname: Lehr
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016682:Lupus Coagulation Inhibitor; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D020125:Mutation, Missense; D016017:Odds Ratio; D019038:Platelet Glycoprotein GPIb-IX Complex; D011110:Polymorphism, Genetic; D011961:Receptors, Fc / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D012306:Risk; D013923:Thromboembolism / Q000209:etiology* / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; C080568:Fc gamma receptor IIA; D016682:Lupus Coagulation Inhibitor; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D011961:Receptors, Fc; D017452:Receptors, IgG; C094990:adhesion receptor