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.

Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes

“…For unknown reasons, humans may 'spontaneously' produce high amounts of neutralizing aAb to a number of growth factors and cytokines, and following the immunological breach the plasma levels of these aAb remain constant over time , Galle et al 2004b. Natural cytokine aAb are found in healthy blood donors and are readily detectable in pharmaceutically prepared pooled normal IgG , Ross et al 1995.…”

“…40) that cause an impairment of the IL6 signaling in vivo (Galle et al 2004b). Very high levels of aAb-IL6 (B/TO0 .…”

“…Substantial high-affinity binding of IL6 is detectable in highly diluted plasma from around 1% of apparently healthy blood donors (Galle et al 2004b). This binding is not related to soluble IL6R compounds but evidently due to nanomolar concentrations of in vitro neutralizing polyclonal IgG autoantibodies (aAb) with very high binding affinity (Hansen et al 1991, Galle et al 2004b.…”

“…This binding is not related to soluble IL6R compounds but evidently due to nanomolar concentrations of in vitro neutralizing polyclonal IgG autoantibodies (aAb) with very high binding affinity (Hansen et al 1991, Galle et al 2004b. In fact, most of these aAb-IL6 are IgG1 antibodies .…”

Beware of Antibodies to Dietary Proteins in “Antigen-specific” Immunoassays! Falsely Positive Anticytokine Antibody Tests Due to Reactivity with Bovine Serum Albumin in Rheumatoid Arthritis (The Swedish TIRA Project)

“…Therapy-induced antibodies to cytokines were generally thought to inhibit cytokine functions, and thus eventually resulting in various degrees of 'cytokine deficiency'. However, when the presence of various naturally occurring anti-cytokine antibodies also became apparent [21,22,29,30], it was proposed that some of these antibodies could serve as specific carriers to deliver cytokines to target cells. Hypothetically, this physiological carrier function could also delay cytokine elimination from the circulation and protect it from proteolytic degradation [28].…”