title: The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation.
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.
authors.affiliation: Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Fickentscher
authors.affiliation: Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany ; Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov Street 14/16, Lviv 79005, Ukraine.
authors.forename: Iryna
authors.initials: I
authors.lastname: Magorivska
authors.affiliation: Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany ; Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), University Hospital, Waldstraße 1/Glückstraße 10, 91054 Erlangen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Janko
authors.affiliation: Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Biermann
authors.affiliation: Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov Street 14/16, Lviv 79005, Ukraine.
authors.forename: Rostyslav
authors.initials: R
authors.lastname: Bilyy
authors.affiliation: Rheumatology and Clinical Immunology, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nalli
authors.affiliation: Rheumatology and Clinical Immunology, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Tincani
authors.affiliation: Paediatric Immunology and Rheumatology, Children's Hospital Brescia, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Medeghini
authors.affiliation: Paediatric Immunology and Rheumatology, Children's Hospital Brescia, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Meini
authors.affiliation: Department of Biology, Institute of Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erwin-Rommel Str. 3, 91058 Erlangen, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
authors.affiliation: Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.affiliation: Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Muñoz
authors.affiliation: Rheumatology and Clinical Immunology, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Andreoli
authors.affiliation: Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
mesh_terms: D000293:Adolescent; D017152:Antibodies, Antiphospholipid / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism; D015932:Complement C3c / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism*; D007075:Immunoglobulin M / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D053482:beta 2-Glycoprotein I / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053482:beta 2-Glycoprotein I; D015922:Complement C1q; D015932:Complement C3c