The FcγRIIa polymorphism R/H131, autoantibodies against the platelet receptors GPIbα and FcγRIIa and a risk for thromboembolism in lupus anticoagulant patients

Katharina Schallmoser; Christiane Rosin; Regina Knittelfelder; Thomas Sailer; Silvia Ulrich; Claudia Zoghlami; Stephan Lehr; Ingrid Pabinger; Simon Panzer

doi:10.1160/TH04-07-0428

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(03): 544-548
DOI: 10.1160/TH04-07-0428

Platelets and Blood Cells

Schattauer GmbH

The FcγRIIa polymorphism R/H131, autoantibodies against the platelet receptors GPIbα and FcγRIIa and a risk for thromboembolism in lupus anticoagulant patients

Katharina Schallmoser

¹Clinic for Blood Group Serology, Medical University of Vienna

²Clinic for Blood Group Serology and Transfusion Medicine, Medical University of Graz

,

Christiane Rosin

¹Clinic for Blood Group Serology, Medical University of Vienna

,

Regina Knittelfelder

¹Clinic for Blood Group Serology, Medical University of Vienna

,

Thomas Sailer

³Department of Internal Medicine, Division of Haematology and Haemostaseology

,

Silvia Ulrich

²Clinic for Blood Group Serology and Transfusion Medicine, Medical University of Graz

,

Claudia Zoghlami

³Department of Internal Medicine, Division of Haematology and Haemostaseology

,

Stephan Lehr

⁴Department of Medical Computer Sciences – Clinical Biometrics, Medical University Vienna, Austria

,

Ingrid Pabinger

³Department of Internal Medicine, Division of Haematology and Haemostaseology

,

Simon Panzer

¹Clinic for Blood Group Serology, Medical University of Vienna

› Author Affiliations

Abstract

Summary

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 FcγRIIa receptor is the only Fc receptor expressed by platelets. As platelets can be activated via this receptor, we have compared gene frequencies of the FcγRIIa 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 FcγRIIa and/or GPIbα, which is in close proximity to the FcγRIIa and interacts with it functionally, and a possible linkage of antibody formation to HLA class II alleles. The FcγRIIa-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 FcγRIIa, 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-FcγRIIa or anti GPIbα autoantibodies and the FcγRIIa -R/H131 polymorphism, nor the incidence of TE, nor HLA class II alleles.

Keywords

Lupus anticoagulant - FcγRIIa receptor - GPIbα - thromboembolic disease

Full Text

References

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