The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation
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....
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/638129 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849307987499286528 |
|---|---|
| author | Christoph Fickentscher Iryna Magorivska Christina Janko Mona Biermann Rostyslav Bilyy Cecilia Nalli Angela Tincani Veronica Medeghini Antonella Meini Falk Nimmerjahn Georg Schett Luis E. Muñoz Laura Andreoli Martin Herrmann |
| author_facet | Christoph Fickentscher Iryna Magorivska Christina Janko Mona Biermann Rostyslav Bilyy Cecilia Nalli Angela Tincani Veronica Medeghini Antonella Meini Falk Nimmerjahn Georg Schett Luis E. Muñoz Laura Andreoli Martin Herrmann |
| author_sort | Christoph Fickentscher |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1fa16a1c75614ed59dbb8c4b18cc1e4f |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-1fa16a1c75614ed59dbb8c4b18cc1e4f2025-08-20T03:54:34ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/638129638129The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc GlycosylationChristoph Fickentscher0Iryna Magorivska1Christina Janko2Mona Biermann3Rostyslav Bilyy4Cecilia Nalli5Angela Tincani6Veronica Medeghini7Antonella Meini8Falk Nimmerjahn9Georg Schett10Luis E. Muñoz11Laura Andreoli12Martin Herrmann13Department for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, GermanyDepartment for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, GermanyDepartment for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, GermanyDepartment for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, GermanyInstitute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov Street 14/16, Lviv 79005, UkraineRheumatology and Clinical Immunology, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, ItalyRheumatology and Clinical Immunology, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, ItalyPaediatric 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, ItalyPaediatric 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, ItalyDepartment of Biology, Institute of Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erwin-Rommel Str. 3, 91058 Erlangen, GermanyDepartment for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, GermanyDepartment for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, GermanyRheumatology and Clinical Immunology, Department of Clinical and Experimental Sciences, Spedali Civili and University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, ItalyDepartment for Internal Medicine 3, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, GermanyTo 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.http://dx.doi.org/10.1155/2015/638129 |
| spellingShingle | Christoph Fickentscher Iryna Magorivska Christina Janko Mona Biermann Rostyslav Bilyy Cecilia Nalli Angela Tincani Veronica Medeghini Antonella Meini Falk Nimmerjahn Georg Schett Luis E. Muñoz Laura Andreoli Martin Herrmann The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation Journal of Immunology Research |
| title | The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation |
| title_full | The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation |
| title_fullStr | The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation |
| title_full_unstemmed | The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation |
| title_short | The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation |
| title_sort | pathogenicity of anti β2gp1 igg autoantibodies depends on fc glycosylation |
| url | http://dx.doi.org/10.1155/2015/638129 |
| work_keys_str_mv | AT christophfickentscher thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT irynamagorivska thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT christinajanko thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT monabiermann thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT rostyslavbilyy thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT cecilianalli thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT angelatincani thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT veronicamedeghini thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT antonellameini thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT falknimmerjahn thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT georgschett thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT luisemunoz thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT lauraandreoli thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT martinherrmann thepathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT christophfickentscher pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT irynamagorivska pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT christinajanko pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT monabiermann pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT rostyslavbilyy pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT cecilianalli pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT angelatincani pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT veronicamedeghini pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT antonellameini pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT falknimmerjahn pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT georgschett pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT luisemunoz pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT lauraandreoli pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation AT martinherrmann pathogenicityofantib2gp1iggautoantibodiesdependsonfcglycosylation |