Intravenous immunoglobulin preparations contain anti–Siglec-8 autoantibodies

• Published in: Journal of allergy and clinical immunology Vol. 119; no. 4; pp. 1005 - 1011
• Main Authors: von Gunten, Stephan, MD, PhD, MME, Vogel, Monique, PhD, Schaub, Alexander, PhD, Stadler, Beda M., PhD, Miescher, Sylvia, PhD, Crocker, Paul R., PhD, Simon, Hans-Uwe, MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.04.2007; Elsevier; Elsevier Limited
• Subjects: Adjuvants, Immunologic - physiology; Allergy and Immunology; Antigens, CD - immunology; Antigens, Differentiation, B-Lymphocyte - immunology; Apoptosis; Apoptosis - immunology; autoantibodies; Autoantibodies - isolation & purification; Autoantibodies - physiology; Biological and medical sciences; Cell Death - immunology; Cells, Cultured; Cloning; Colleges & universities; Cytotoxicity; eosinophils; Eosinophils - immunology; Eosinophils - pathology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte-Macrophage Colony-Stimulating Factor - physiology; Humans; Hypereosinophilic Syndrome - immunology; Hypereosinophilic Syndrome - pathology; Immunoglobulins, Intravenous - chemistry; Immunoglobulins, Intravenous - physiology; Immunoglobulins, Intravenous - toxicity; Immunopathology; inflammation; Interleukin-5 - physiology; IVIg; Lectins - immunology; Leptin - physiology; Ligands; Medical sciences; Molecular weight; Proteins; Siglec-8; Statistical analysis; Switzerland; NADPH; Reactive oxygen species; Siglec; Intravenous immunoglobulin; eosinophils; IVIg; MIF; Siglec-8; Macrophage migration inhibitory factor; NAC; Diphenyleneiodonium; N-benzyloxycarbonyl (z)-Val-Ala-Asp-fluormethylketone (fmk); inflammation; Nicotinamide adenine dinucleotide phosphate; Sialic acid-binding immunoglobulin-like lectin; HES; ROS; VAD; N-Acetyl-L-cysteine; DPI; autoantibodies; Apoptosis; Hypereosinophilic syndrome; Autoimmunity; Immunopathology; Immunoglobulins; Intravenous administration; Antibody; Granulocyte; Autoantibody; Inflammation; Eosinophil; Immunology; Cell death; Sialic acid binding immunoglobulin like lectin 8
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.01.023

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-γ, TNF-α, 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.