The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation.

Christoph Fickentscher,Angela Tincani,Georg Schett,Falk Nimmerjahn,Antonella Meini,Martin Herrmann,Christina Janko,Iryna Magorivska,Rostyslav Bilyy,Cecilia Nalli,Luis E Muñoz,Mona Biermann,Laura Andreoli,Veronica Medeghini

doi:10.1155/2015/638129

Abstract

To analyze the glycosylation of anti-β2GP1, we investigated purified IgG from healthy children, patients with APS, and asymptomatic adult carriers of antiphospholipid antibodies. We observed that in the sera of healthy children and of patients with APS, IgG3 and IgG2 were predominant, respectively. The potentially protective anti-β2GP1-IgM was lower in the sera of healthy children. Although anti-β2GP1-associated C1q did not differ between children and patients with antiphospholipid syndrome, the associated C3c was significantly higher in the sera of healthy children. This indicates a more efficient clearance of anti-β2GP1 immune complexes in the healthy children. This clearance is not accompanied by inflammation or coagulatory events. It is likely that the most important pathogenic factor of the anti-β2GP1-IgG is related to the different glycosylation observed in healthy and diseased individuals. We detected a significantly higher sialylation of anti-β2GP1-IgG isolated from the sera of healthy children and asymptomatic adults when compared with that of patients with clinically apparent antiphospholipid syndrome. Low sialylated IgG reportedly ameliorates inflammation and inflammation promotes hyposialylation. Thus, both reactions create a vicious circle that precipitates the pathology of the antiphospholipid syndrome including thrombus-formation. We conclude that the increased sialylation of anti-β2GP1-IgG of sera of healthy individuals limits their pathogenicity.

Highlights

The antiphospholipid syndrome (APS) is an autoimmune disease affecting the coagulation system
Thrombosis as one major symptom in APS is mainly associated with anti-β2GP1 [3]. β2GP1 is a plasma protein Journal of Immunology Research composed of five domains [4] and it is known to be an inhibitor of the contact activation of the intrinsic coagulation pathway [5]
Patients with APS can be classified into two groups depending on the occurrence of further diseases: (I) patients merely suffering from APS and (II) those with an underlying systemic lupus erythematodes (SLE)

Summary

Introduction

The antiphospholipid syndrome (APS) is an autoimmune disease affecting the coagulation system. The serological criteria include the detection of so-called antiphospholipid antibodies (aPL) which comprise the lupus anticoagulant (LA), anticardiolipin autoantibodies (aCL), and anti-β2-glycoprotein 1 autoantibodies (anti-β2GP1) [1]. Patients with APS can be classified into two groups depending on the occurrence of further diseases: (I) patients merely suffering from APS (primary antiphospholipid syndrome; PAPS) and (II) those with an underlying systemic lupus erythematodes (SLE). The latter condition is referred to as secondary antiphospholipid syndrome (SAPS) [8]

Methods

Results

Conclusion