High levels of neutralizing IL-6 autoantibodies in 0.1% of apparently healthy blood donors

TY - JOUR

T1 - High levels of neutralizing IL-6 autoantibodies in 0.1% of apparently healthy blood donors

AU - Galle, Pia

AU - Svenson, Morten

AU - Bendtzen, Klaus

AU - Hansen, Morten B

PY - 2004/11/1

Y1 - 2004/11/1

N2 - 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.

AB - 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.

U2 - http://dx.doi.org/10.1002/eji.200425268

DO - http://dx.doi.org/10.1002/eji.200425268

M3 - Journal article

SN - 0014-2980

VL - 34

SP - 3267

EP - 3275

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 11

ER -