title: High levels of neutralizing IL-6 autoantibodies in 0.1% of apparently healthy blood donors.
abstract: IL-6-specific autoantibodies (aAb-IL-6) have been reported in diseased and healthy individuals. We recently established a model for aAb-IL-6 in different mouse strains, based on vaccination with immunogenic IL-6 analogues, in which titers of aAb-IL-6 above 1,000 resulted in an in vivo IL-6 deficiency. Here, we examined aAb-IL-6 in 4,230 blood donors. Stable low titers of aAb-IL-6 were found in 9% of the donors, while 1% had titers ranging from 64 to greater than 10,000. Such aAb-IL-6-positive donors appeared normal with no overt signs of pathology. Natural and recombinant forms of IL-6 bound avidly to their IgG, and their plasma strongly neutralized IL-6 in vitro. Slightly elevated concentrations of IL-6 exclusively in the form of IL-6-IgG complexes were present in their circulation. The complexes did not contain soluble IL-6 receptors. Titers of 0.1% of the blood donors were as positive as the vaccination-induced IL-6-deficient mice. Such donors might be IL-6 deficient, and if so, IL-6 seems be dispensable for several months in otherwise healthy individuals. Such highly positive donors also explain why normal human IgG for pharmaceutical use may contain high anti-IL-6 activity. Finally, transfusion of plasma with a high titer of aAb-IL-6 might, temporally, render a recipient IL-6 deficient.
authors.affiliation: Institute for Inflammation Research, Rigshospitalet, National University Hospital, Copenhagen, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Galle
authors.forename: Morten
authors.initials: M
authors.lastname: Svenson
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Morten B
authors.initials: MB
authors.lastname: Hansen
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001681:Biological Assay; D001782:Blood Donors; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000276:immunology; D015850:Interleukin-6 / Q000172:deficiency / Q000276:immunology*; D008297:Male; D051379:Mice; D011863:Radioimmunoassay; D019947:Receptors, Interleukin-6 / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D015850:Interleukin-6; D019947:Receptors, Interleukin-6