Intravenous immunoglobulin preparations contain anti-Siglec-8 autoantibodies.
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.


CONCLUSIONS
IVIg preparations contain natural anti-Siglec-8 autoantibodies.


CONCLUSIONS
Anti-Siglec-8 autoantibodies present in IVIg preparations may have therapeutic relevance in autoimmune and allergic diseases, respectively, such as Churg-Strauss syndrome.
von Gunten
Stephan
S
Department of Pharmacology, University of Bern, Bern, Switzerland.
Vogel
Monique
M
Schaub
Alexander
A
Stadler
Beda M
BM
Miescher
Sylvia
S
Crocker
Paul R
PR
Simon
Hans-Uwe
HU
D000276:Adjuvants, Immunologic / Q000502:physiology; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000302:isolation & purification / Q000502:physiology*; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000276:immunology / Q000473:pathology; D016756:Immunoglobulins, Intravenous / Q000737:chemistry* / Q000502:physiology* / Q000633:toxicity; D015848:Interleukin-5 / Q000502:physiology; D037102:Lectins / Q000276:immunology*; D020738:Leptin / Q000502:physiology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D001323:Autoantibodies; D016756:Immunoglobulins, Intravenous; D015848:Interleukin-5; D037102:Lectins; D020738:Leptin; C403967:SIGLEC8 protein, human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor