Intravenous immunoglobulin preparations contain anti-Siglec-8 autoantibodies

von Gunten, Stephan; Vogel, Monique; Schaub, Alexander; Stadler, Beda M; Miescher, Sylvia; Crocker, Paul R; Simon, Hans-Uwe (2007). Intravenous immunoglobulin preparations contain anti-Siglec-8 autoantibodies. Journal of allergy and clinical immunology, 119(4), pp. 1005-11. St. Louis, Mo.: Mosby 10.1016/j.jaci.2007.01.023

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BACKGROUND: Human intravenous immunoglobulin (IVIg) preparations are used for the treatment of autoimmune and allergic diseases. Natural autoantibodies are believed to contribute to IVIg-mediated anti-inflammatory effects. OBJECTIVE: To address the question of whether IVIg preparations contain anti-sialic acid-binding Ig-like lectin-8 (anti-Siglec-8) autoantibodies. METHODS: The presence of possible anti-Siglec-8 autoantibodies in IVIg preparations was first examined by functional eosinophil death and apoptosis assays. Specificity of IVIg effects was shown by depleting anti-Siglec-8 autoantibodies from IVIg. Binding of purified anti-Siglec-8 autoantibodies to recombinant Siglec-8 was demonstrated by an immunodot assay. RESULTS: IVIg exerts cytotoxic effects on purified human blood eosinophils. Both potency and efficacy of the IVIg-mediated eosinophil killing effect was enhanced by IL-5, granulocyte/macrophage colony-stimulating factor, IFN-gamma, TNF-alpha, and leptin. Similarly, inflammatory eosinophils obtained from patients suffering from the hypereosinophilic syndrome (HES) demonstrated increased Siglec-8 cytotoxic responses when compared with normal blood eosinophils. Pharmacologic blocking experiments indicated that the IVIg-mediated additional eosinophil death in the presence of cytokines is largely caspase-independent, but it depends on reactive oxygen species. Anti-Siglec-8 autoantibody-depleted IVIg failed to induce caspase-independent eosinophil death. CONCLUSION: IVIg preparations contain natural anti-Siglec-8 autoantibodies. CLINICAL IMPLICATIONS: Anti-Siglec-8 autoantibodies present in IVIg preparations may have therapeutic relevance in autoimmune and allergic diseases, respectively, such as Churg-Strauss syndrome.

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

von Gunten, Stephan; Vogel, Monique; Stadler, Beda Martin; Miescher-Granger, Sylvia M. and Simon, Hans-Uwe

ISSN:

0091-6749

ISBN:

17337295

Publisher:

Mosby

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:54

Last Modified:

04 May 2014 23:15

Publisher DOI:

10.1016/j.jaci.2007.01.023

PubMed ID:

17337295

Web of Science ID:

000245729500033

URI:

https://boris.unibe.ch/id/eprint/23012 (FactScience: 38549)

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