Immunologic and functional evidence for anti-Siglec-9 autoantibodies in intravenous immunoglobulin preparations

von Gunten, Stephan; Schaub, Alexander; Vogel, Monique; Stadler, Beda M; Miescher, Sylvia; Simon, Hans-Uwe (2006). Immunologic and functional evidence for anti-Siglec-9 autoantibodies in intravenous immunoglobulin preparations. Blood, 108(13), pp. 4255-9. Washington, D.C.: American Society of Hematology 10.1182/blood-2006-05-021568

Full text not available from this repository. (Request a copy)

Human intravenous immunoglobulin (IVIg) preparations are increasingly used for the treatment of autoimmune diseases. Earlier work demonstrated the presence of autoantibodies against Fas in IVIg, suggesting that IVIg might be able to induce caspase-dependent cell death in Fas-sensitive cells. In this study, we demonstrate that sialic acid-binding Ig-like lectin 9 (Siglec) represents a surface molecule on neutrophils that is activated by IVIg, resulting in caspase-dependent and caspase-independent forms of cell death. Neutrophil death was mediated by naturally occurring anti-Siglec-9 autoantibodies present in IVIg. Moreover, the efficacy of IVIg-mediated neutrophil killing was enhanced by the proinflammatory cytokines granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma), and this additional cell death required reactive oxygen species (ROSs) but not caspases. Anti- Siglec-9 autoantibody-depleted IVIg failed to induce this caspase-independent neutrophil death. These findings contribute to our understanding of how IVIg preparations exert their immunoregulatory effects under pathologic conditions and may provide a possible explanation for the neutropenia that is sometimes seen in association with IVIg therapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology (discontinued)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Vogel, Monique; Stadler, Beda Martin and Simon, Hans-Uwe

ISSN:

0006-4971

ISBN:

16902148

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

04 May 2014 23:13

Publisher DOI:

10.1182/blood-2006-05-021568

PubMed ID:

16902148

Web of Science ID:

000242675300049

URI:

https://boris.unibe.ch/id/eprint/18762 (FactScience: 1000)

Actions (login required)

Edit item Edit item
Provide Feedback